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1. Regional Metabolic Disturbances and Cerebrovascular Anatomy after Permanent Middle Cerebral Artery Occlusion in C57Black/6 and SV129 Mice

Author

K. Maeda, R. Hata, and K.-A. Hossmann

Subjects
brain angioarchitecture, collateral circulation, cerebral infarction, blood flow, penumbra, ATP imaging, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

C57Black/6 and SV129 mice are widely used for the production of transgenic mutants in molecular stroke research but the ischemic susceptibility of these strains is influenced by differences in vascular anatomy and the responsiveness to excitotoxins and vasodilatory stimuli. To differentiate between these opposing effects on infarct size, the vascular territory of the two strains was correlated with the hemodynamic, metabolic, and morphological consequences of permanent middle cerebral artery (MCA) occlusion. The vascular anatomy was studied by latex infusion, brain infarction by vital staining, the size of the ischemic penumbra by imaging of ATP and protein synthesis, and blood flow by laser–Doppler flowmetry. In C57Black/6 mice the MCA-supplied vascular territory and the size of brain infarcts were significantly larger than in SV129 mice but the size of the penumbra and the residual blood flow in the center of the MCA-supplying territory were similar in both strains. These findings suggest that differences in infarct size in C57Black/6 and SV129 mice are determined mainly by the vascular anatomy and not by differences in collateral vascular responsiveness or excitotoxicity.

Published
1999
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2. Thrombolysis for Prevention of Cerebral No-Reflow After Cardiopulmonary Resuscitation

Author

K. -A. Hossmann, V. Hossmann, and B. W. Bottiger

Subjects
cardiac arrest, no-reflow phenomenon, neurological recovery, disseminated intravascular coagulation, thrombolysis., Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Thrombolytic treatment during cardiopulmonary resuscitation is thought to reverse the cerebral no-reflow phenomenon which is widely considered to limit neurological recovery after prolonged cardio-circulatory arrest. However, the recent multicenter randomized double-blind TROICA (Thrombolysis in Cardiac Arrest) trial revealed that patients with witnessed out-of-hospital cardiac arrest did not experience an improvement of neurological outcome when treated with the throm-bolytic agent tenecteplase [1]. This raises the question of the importance of coagulation disturbances in the pathophysiol-ogy of no-reflow and its reversal by thrombolytic interventions. This article provides an overview of the experimental literature on this subject.

Published
2009
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7. Differences in Clot Preparation Determine Outcome of Recombinant Tissue Plasminogen Activator Treatment in Experimental Thromboembolic Stroke

Author

K.-A. Hossmann, Mathias Hoehn, Thomas Hilger, and Frank Niessen

Subjects
Gadolinium DTPA, Male, Time Factors, medicine.medical_treatment, Thromboembolic stroke, Fibrin, Adenosine Triphosphate, medicine, Animals, Thrombolytic Therapy, Rats, Wistar, Stroke, Cerebral Hemorrhage, Advanced and Specialized Nursing, biology, T-plasminogen activator, business.industry, Thrombin, Brain, Infarction, Middle Cerebral Artery, Thrombolysis, medicine.disease, Elasticity, Recombinant Proteins, Rats, Disease Models, Animal, Treatment Outcome, Embolism, Blood-Brain Barrier, Cerebrovascular Circulation, Tissue Plasminogen Activator, Anesthesia, Reperfusion, Disease Progression, biology.protein, Arterial blood, Neurology (clinical), Intracranial Thrombosis, Cardiology and Cardiovascular Medicine, business, Perfusion, Magnetic Resonance Angiography, Extravasation of Diagnostic and Therapeutic Materials
Abstract

Background and Purpose— Thrombin-induced clots used in experimental thromboembolic stroke differ from clots forming spontaneously under clinical conditions. We investigated whether this difference influences the efficacy and outcome of thrombolytic treatment. Methods— In rats, the middle cerebral artery was occluded by intracarotid injection of fibrin-rich clots, prepared either according to established methods by adding thrombin to freshly drawn arterial blood or by spontaneous coagulation. The mechanical properties of clots were determined in vitro by elasticity and plasticity tests. One hour after embolism, thrombolysis was started by intra-arterial application of recombinant tissue plasminogen activator (rtPA) (10 mg/kg). Treatment efficacy was monitored by MR measurements of blood perfusion, apparent diffusion coefficient (ADC), T2 relaxation time and blood-brain barrier permeability, and by pictorial measurements of ATP and pH. Results— Thrombin-induced clots were classified as elastic, and spontaneously forming clots were classified as plastic. Middle cerebral artery embolism with thrombin-induced or spontaneously forming clots led to similar reduction of perfusion and ADC, but rtPA treatment efficacy differed greatly. In the spontaneously forming clot group, blood perfusion returned to or above control within 2 hours, ADC and ATP normalized, tissue pH exhibited alkalosis, and T2 and blood-brain barrier permeability did not change. In the thrombin-induced clot group, in contrast, blood reperfusion was delayed, ADC and ATP remained reduced, tissue pH was acidic, and edema developed, as reflected by increased T2 and blood-brain barrier permeability. Conclusions— rtPA-induced thrombolysis promotes rapid reperfusion and tissue recovery in animals embolized with spontaneously forming clots but not in those embolized with thrombin-induced clots. This difference is explained by the different mechanical and possibly molecular consequences of clot preparation and must be considered for the interpretation of thrombolysis experiments.

Published
2003
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8. Effects of electromagnetic radiation of mobile phones on the central nervous system

Author

K.-A. Hossmann and Dirk M. Hermann

Subjects
Radio Waves, Physiology, Central nervous system, Biophysics, Energy metabolism, Electromagnetic Fields, medicine, Animals, Humans, Radiology, Nuclear Medicine and imaging, Telephony, Health risk, Brain Neoplasms, Human organism, business.industry, Brain, Electroencephalography, DNA, General Medicine, Telephone, Radio frequency radiation, medicine.anatomical_structure, Blood-Brain Barrier, Mobile telephony, Barrier permeability, Sleep, business, Neuroscience
Abstract

With the increasing use of mobile communication, concerns have been expressed about the possible interactions of electromagnetic radiation with the human organism and, in particular, the brain. The effects on neuronal electrical activity, energy metabolism, genomic responses, neurotransmitter balance, blood-brain barrier permeability, cognitive function, sleep, and various brain diseases including brain tumors are reviewed. Most of the reported effects are small as long as the radiation intensity remains in the nonthermal range, and none of the research reviewed gives an indication of the mechanisms involved at this range. However, health risks may evolve from indirect consequences of mobile telephony, such as the sharply increased incidence rate of traffic accidents caused by telephony during driving, and possibly also by stress reactions which annoyed bystanders may experience when cellular phones are used in public places. These indirect health effects presumably outweigh the direct biological perturbations and should be investigated in more detail in the future.

Published
2002
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9. Neuron-to-astrocyte signaling is central to the dynamic control of brain microcirculation

Author

Bernhard Rosengarten, Giorgio Carmignoto, Sara Gobbo, K.-A. Hossmann, María Cecilia Angulo, Tullio Pozzan, and Micaela Zonta

Subjects
Vasodilator Agents, Gliotransmitter, Glutamic Acid, Vasodilation, Cell Communication, Nitric Oxide, Receptors, Metabotropic Glutamate, Somatosensory system, Microcirculation, medicine, Animals, Premovement neuronal activity, Calcium Signaling, Enzyme Inhibitors, Rats, Wistar, Cerebral Cortex, Neurons, Afferent Pathways, Chemistry, General Neuroscience, Brain, Electric Stimulation, Rats, medicine.anatomical_structure, Animals, Newborn, Cerebral cortex, Astrocytes, Cerebrovascular Circulation, Neuron, Excitatory Amino Acid Antagonists, Neuroscience, Signal Transduction, Astrocyte
Abstract

The cellular mechanisms underlying functional hyperemia--the coupling of neuronal activation to cerebral blood vessel responses--are not yet known. Here we show in rat cortical slices that the dilation of arterioles triggered by neuronal activity is dependent on glutamate-mediated [Ca(2+)](i) oscillations in astrocytes. Inhibition of these Ca(2+) responses resulted in the impairment of activity-dependent vasodilation, whereas selective activation--by patch pipette--of single astrocytes that were in contact with arterioles triggered vessel relaxation. We also found that a cyclooxygenase product is centrally involved in this astrocyte-mediated control of arterioles. In vivo blockade of glutamate-mediated [Ca(2+)](i) elevations in astrocytes reduced the blood flow increase in the somatosensory cortex during contralateral forepaw stimulation. Taken together, our findings show that neuron-to-astrocyte signaling is a key mechanism in functional hyperemia.

Published
2002
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10. Delayed Neuronal Death After Brief Histotoxic Hypoxia In Vitro

Author

A. Uto, E. Dux, M. Kusumoto, and K.-A. Hossmann

Subjects
Programmed cell death, Potassium cyanide, chemistry.chemical_element, Iodoacetates, Nerve Tissue Proteins, Pharmacology, Biology, Calcium, Hippocampus, Biochemistry, Calcium in biology, Cellular and Molecular Neuroscience, chemistry.chemical_compound, medicine, Animals, Vitamin E, Rats, Wistar, Potassium Cyanide, Histotoxic hypoxia, Cells, Cultured, Cerebral Cortex, Neurons, Cell Death, Adenine Nucleotides, Glutamate receptor, medicine.disease, Free radical scavenger, Cell Hypoxia, Iodoacetic Acid, Rats, medicine.anatomical_structure, nervous system, chemistry, Arsenates, Neuron, Dizocilpine Maleate, Energy Metabolism
Abstract

The effect of three metabolic inhibitors--iodoacetate, potassium cyanide, and potassium arsenate--on neuronal viability was studied in primary rat cortical and hippocampal CA1 neuronal cultures. Iodoacetate (0.1 mM) applied for 5 min to 8-day-old cultures resulted in delayed neuronal death within 3-24 h in cortical and hippocampal CA1 neurons. Neuronal degeneration was preceded by transient inhibition of energy metabolism to approximately 40% and a permanent inhibition of protein synthesis to approximately 50%. The inhibition of protein synthesis and the neuronal death were prevented by the free radical scavenger vitamin E but not by the glutamate antagonist MK-801. Removal of calcium during iodoacetate exposure could not protect against toxicity, and there was no increase of intracellular calcium concentration during and shortly after iodoacetate treatment. Cyanide and arsenate produced only partial neuronal degeneration, even at a dose of 10 mM. These observations demonstrate that brief exposure of neurons to low concentrations of iodoacetate produces a delayed type of neuronal death that is not mediated by either calcium or glutamate. The therapeutic effect of vitamin E points to a free-radical mediated injury and suggests that this type of pathology may also be involved in delayed neuronal death after transient energy depletion in vivo.

Published
2002
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11. Electron microscopic investigation of rat brain after brief cardiac arrest

Author

K.-A. Hossmann, U. Oschlies, Henning Krep, and W. Schwindt

Subjects
Pathology, medicine.medical_specialty, Nuclear Envelope, Thalamus, Central nervous system, Hippocampal formation, Biology, Brain Ischemia, Pathology and Forensic Medicine, Cardiovascular Physiological Phenomena, Cyclic N-Oxides, Brain ischemia, Cellular and Molecular Neuroscience, medicine, Animals, Cell Size, Cell Nucleus, Neurons, Organelles, Dentate gyrus, Brain, medicine.disease, Chromatin, Capillaries, Heart Arrest, Rats, Microscopy, Electron, Neuroprotective Agents, medicine.anatomical_structure, nervous system, Cerebral cortex, Nerve Degeneration, Reticular connective tissue, Nitrogen Oxides, Neurology (clinical), Neuroglia, Pyknosis
Abstract

Rats were submitted to 10-min cardiac arrest, followed by resuscitation and survival for 1 day, 3 days or 1 week. Five regions of interest (CA1 and CA3 sector of hippocampus, dentate gyrus, reticular nucleus of thalamus and parietal cortex) where studied by light and electron microscopy at each of the survival times, and compared with non-ischemic control rats. Cell counts revealed delayed neuronal loss of about 30% after 3 days in both CA1 and CA3 sectors. Ischemic cell changes consisting of cytoplasmic condensation and nuclear pyknosis appeared in these regions on day 7 and --to a lesser degree-- also affected dentate gyrus, the reticular nucleus of thalamus and cerebral cortex. Ultrastructural alterations were evaluated using an ultrastructural injury catalogue. In all brain regions similar, although quantitatively differently expressed, changes occurred except ribosomal disaggregation, which was restricted to neurons of hippocampal CA1 sector on the first day after cardiac arrest. Progressive alterations included swelling of mitochondria and endoplasmic reticulum, which was most pronounced in CA1 and CA3 sectors of hippocampus, as well as chromatin aggregation and alterations of neuronal volume, which affected mainly the granule cells of dentate gyrus. Other alterations, such as osmiophilic inclusions or the formation of nuclear pore complexes, were transient with a maximum on the first day after cardiac arrest. Treatment with the free-radical scavenger alpha-phenyl-N-tert-butyl nitrone (PBN) suppressed the formation of nuclear pores but otherwise did not markedly change the morphological outcome. In comparison to previous studies of global brain ischemia induced by arterial inflow occlusion of the same duration, the present data demonstrate remarkable preservation of tissue integrity in CA1 sector but also distinct changes in brain regions considered to be resistant to ischemic injury. Morphological alterations of brain after cardiac arrest do not follow the established pattern of selective vulnerability.

Published
2001
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12. Biphasic expression of TGF-β1 mRNA in the rat brain following permanent occlusion of the middle cerebral artery

Author

Peter Vogel, Christoph Wiessner, K.-A. Hossmann, Katsuhiro Yamashita, and U Gerken

Subjects
Male, Cingulate cortex, medicine.medical_specialty, Ischemia, Arterial Occlusive Diseases, Glial scar, chemistry.chemical_compound, Downregulation and upregulation, Transforming Growth Factor beta, Quinoxalines, medicine.artery, Internal medicine, medicine, Animals, RNA, Messenger, cardiovascular diseases, Molecular Biology, business.industry, General Neuroscience, Glutamate receptor, Brain, Depolarization, Cerebral Arteries, medicine.disease, Rats, Inbred F344, Rats, Endocrinology, chemistry, Chronic Disease, Middle cerebral artery, NBQX, Neurology (clinical), Dizocilpine Maleate, business, Excitatory Amino Acid Antagonists, Neuroscience, Developmental Biology
Abstract

Two patterns of transforming growth factor-beta1 (TGF-beta1) expression were identified in brains of normotensive rats following permanent occlusion of the middle cerebral artery (MCAO). First, a relative increase of TGF-beta1 mRNA by 37% was found at 12 h after MCAO in the ipsilateral cingulate cortex as compared to the homotopic contralateral region. The cingulate cortex is located distant from the ischemic territory. Treatment with the glutamate receptor antagonists MK-801 and NBQX did not reduce this expression (34% and 26% increase, respectively). Therefore, peri-infarct depolarization waves were probably not responsible for induction. Secondly, an increase of TGF-beta1 mRNA by 116% was found at 7 days after MCAO within infarcted tissue. This expression was not reduced by the glutamate receptor antagonists MK-801 (increase 140%) and NBQX (increase 137%), either. TGF-beta1 mRNA expression in the cingulate cortex at 12 h after MCAO is possibly mediated by neurons and astroglia and may support cell survival. Expression in the infarcted tissue at 7 days after MCAO is most likely related to the invasion of monocytes and may be involved in the downregulation of inflammatory events, in neoangiogenesis, and in formation of a glial scar around the infarct.

Published
1999
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13. Recombinant tissue plasminogen activator reduces infarct size after reversible thread occlusion of middle cerebral artery in mice

Author

Ertugrul Kilic, Dirk M. Hermann, and K.-A. Hossmann

Subjects
medicine.medical_specialty, Pathology, Cerebral arteries, Drug Evaluation, Preclinical, Ischemia, Arterial Occlusive Diseases, Vascular occlusion, Tissue plasminogen activator, Mice, Internal medicine, medicine.artery, Occlusion, Laser-Doppler Flowmetry, medicine, Animals, Stroke, T-plasminogen activator, business.industry, General Neuroscience, Cerebral Infarction, medicine.disease, Recombinant Proteins, Mice, Inbred C57BL, Neuroprotective Agents, Tissue Plasminogen Activator, Middle cerebral artery, Cardiology, medicine.symptom, business, medicine.drug
Abstract

It has been suggested that tissue plasminogen activator (tPA), which is widely used for the thrombolytic treatment of stroke, exhibits neurotoxic side effects. To test this hypothesis, mice exposed to 90 min nonthrombotic middle cerebral artery thread occlusion were treated with 10 mg/kg recombinant tPA (rt-PA) at 15 min after the onset of vascular occlusion. Measurements of blood flow, infarct volume, brain swelling and neurological performance revealed faster recirculation and a significant reduction of ischemic injury in rt-PA-treated animals. These data are at variance with previous reports on tPA neurotoxicity and demonstrate, on the contrary, that tPA protects the brain even after non-thrombotic vascular occlusion.

Published
1999
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14. Expression of c-fos, junB, c-jun, MKP-1 AND hsp72 following traumatic neocortical lesions in rats—relation to spreading depression

Author

Günter Mies, Dirk M. Hermann, and K.-A. Hossmann

Subjects
Male, medicine.medical_specialty, Proto-Oncogene Proteins c-jun, JUNB, Gene Expression, Cell Cycle Proteins, HSP72 Heat-Shock Proteins, Neocortex, Hippocampal formation, c-Fos, Immediate-Early Proteins, Rats, Sprague-Dawley, Protein Phosphatase 1, Piriform cortex, Internal medicine, Laser-Doppler Flowmetry, Phosphoprotein Phosphatases, medicine, Animals, RNA, Messenger, Heat-Shock Proteins, In Situ Hybridization, Brain Chemistry, Neurons, biology, General Neuroscience, Dentate gyrus, Cortical Spreading Depression, c-jun, Dual Specificity Phosphatase 1, Immunohistochemistry, Rats, Electrophysiology, medicine.anatomical_structure, Endocrinology, Cerebral cortex, Cerebrovascular Circulation, Cortical spreading depression, biology.protein, Protein Tyrosine Phosphatases, Proto-Oncogene Proteins c-fos, Neuroscience
Abstract

The effects of a traumatic neocortical lesion on c-fos, junB, c-jun, MKP-1 and hsp72 expression were examined by in situ hybridization and immunocytochemistry 1-6 h following transcranial cold injury. The direct current potential was recorded in the injury-remote cortex to evaluate the role of transient direct current shifts, i.e. spreading depressions, in gene expression. In 14 out of 21 injured rats, spreading depression-like depolarizations of the direct current potential were noticed, which were accompanied by a transient decrease in electroencephalographic activity and increase in laser Doppler flow. In seven injured animals, no spontaneous spreading depressions were seen. In animals without spreading depressions, only a short-lasting response of c-fos, junB, c-jun and MKP-1 messenger RNAs as well as c-Fos protein was bilaterally found in the piriform cortex, and--with ipsilateral dominance--the dentate gyrus and hippocampal CA3/4 fields at 1 h after lesioning. In injured animals with spreading depressions however, a strong elevation was seen in layers II-IV and VI of the injury-remote ipsilateral cerebral cortex, which persisted over as long as 6 h. Messenger RNA levels for c-fos, junB and MKP-1 were closely related to the time interval between the last depolarization and the end of experiment. Levels were highest shortly after transient direct current shifts, and decreased thereafter mono-exponentially with half-lives of 48, 75 and 58 min for c-fos, junB and MKP-1 messenger RNAs, respectively. In 6 h animals with spreading depressions, hsp72 messenger RNA was slightly elevated in layer II of the injury-remote cortex, but heat shock protein 72 was not increased. The present results demonstrate that spreading depression is the most prominent factor influencing the trauma-related gene response in the lesion-remote cortical tissue.

Published
1999
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15. Brain and Heart Infarct II

Author

K.J. Zülch, W. Kaufmann, K.-A. Hossmann, V. Hossmann, K.J. Zülch, W. Kaufmann, K.-A. Hossmann, and V. Hossmann

Subjects
Neurology, Neurosciences
Abstract

Dr. Kaufmann and I wish to welcome you here in Schloss Auel to this second symposium on brain and heart infarct. We have chosen this lovely castle because I am always dissatisfied with meetings in great hotels in cities, where we rush to and from the meeting rooms. I had such an experience overseas just 3 weeks ago from 8 o'clock in the morning until 10 o'clock at night. We want you to feel some of the wonderful atmosphere of the Bergisches La~d. Moreover, we wanted like you to enjoy a bit of the spirit of the Rhein valley and the 2000-year-old city of Cologne, even at the expense of losing a few hours of discus­ sion; though this may be a quantitative loss, we feel sure that the environment of this city will stimulate our discussions. Two years ago we gathered here in Schloss Auel for the first time, attempting to conduct a discussion between neurologists and cardiologists on the similarities and dissimilarities of circulatory disorders of the brain and heart. We are happy to continue this discussi?n in the days to come.

Published
2012

16. Recovery of the rodent brain after cardiac arrest: A functional mri study

Author

B, Schmitz, C, Bock, M, Hoehn-Berlage, C M, Kerskens, B W, Böttiger, and K A, Hossmann

Subjects
Male, medicine.medical_specialty, Pathology, Magnetic Resonance Spectroscopy, Time Factors, Resuscitation, Perfusion scanning, Somatosensory system, Rats, Sprague-Dawley, Evoked Potentials, Somatosensory, Internal medicine, medicine, Animals, Radiology, Nuclear Medicine and imaging, Brain Chemistry, Cerebral Cortex, Blood-oxygen-level dependent, business.industry, Brain, Blood flow, Oxygenation, Magnetic Resonance Imaging, Heart Arrest, Rats, medicine.anatomical_structure, Cerebral cortex, Cerebrovascular Circulation, Circulatory system, Cardiology, business, Perfusion
Abstract

Recovery of the cerebral cortex after 10 min of cardiac arrest was studied in rat using noninvasive MRI techniques. The apparent diffusion coefficient (ADC) of brain water was imaged to document reversal of the metabolic impairment. Perfusion-weighted imaging and blood oxygen level dependent (BOLD) imaging were performed to assess functional recovery. To this purpose, rats were anesthetized with alpha-chloralose, and somatosensory cortex was activated by electrical stimulation of the contralateral forepaw. In sham-operated controls, cortical ADC was 862 +/- 10 microm2/s, and stimulation of forepaw led to a focal increase of signal intensity in somatosensory cortex by 71 +/- 22% in perfusion-weighted images and by 6 +/- 1% in BOLD images. One hour after successful resuscitation following 10 min of cardiac arrest, ADC did not differ from control but functional activation was completely suppressed. After 3 hours of reperfusion, functional activity began to reappear but the recovery of the BOLD signal progressed faster than that of the perfusion-weighted signal. The differences in the recovery of ADC, BOLD, and perfusion imaging are related to differences between metabolic and functional recovery on one hand and between blood flow and oxygen extraction on the other. The combination of these MRI methods thus provides detailed qualitative information about the progression of brain recovery after transient circulatory arrest.

Published
1998
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17. Induction of protein inhibitor of neuronal nitric oxide synthase/cytoplasmic dynein light chain following cerebral ischemia

Author

K.-A. Hossmann, Bernd W. Böttiger, Frank Gillardon, Gerrit Brinker, C Lenz, and Henning Krep

Subjects
Male, Ischemia, Brain Ischemia, Nitric oxide, Rats, Sprague-Dawley, chemistry.chemical_compound, medicine, Animals, Drosophila Proteins, Tissue Distribution, RNA, Messenger, In Situ Hybridization, Messenger RNA, Neocortex, Cell Death, biology, General Neuroscience, Dentate gyrus, NADPH Dehydrogenase, Brain, Dyneins, Blotting, Northern, medicine.disease, Granule cell, Rats, Cell biology, Nitric oxide synthase, medicine.anatomical_structure, nervous system, Biochemistry, chemistry, Enzyme inhibitor, biology.protein, Autoradiography, Carrier Proteins
Abstract

Administration of inhibitors of neuronal nitric oxide synthase or deletion of the encoding gene in rodents provided evidence that neuronal nitric oxide synthase activity may contribute to neuronal cell death following global and focal cerebral ischemia. In the present study, we investigated by in situ hybridization the expression of an endogenous inhibitor of neuronal nitric oxide synthase activity, designated protein inhibitor of neuronal nitric oxide synthase and homologous to cytoplasmic dynein light chain, in the post-ischemic rat brain. Following global ischemia induced by cardiac arrest, messenger RNA expression of protein inhibitor of neuronal nitric oxide synthase was rapidly induced in pyramidal neurons of the hippocampal CA3 region and granule cell of the dentate gyrus which are resistant to ischemic damage. In vulnerable CA1 pyramidal neurons however, protein inhibitor of neuronal nitric oxide synthase expression remained at basal level after global ischemia and was associated with an increase in nicotinamide adenine dinucleotide phosphate-diaphorase activity and subsequent DNA fragmentation indicating ischemia-mediated neuronal cell death. Following focal cerebral ischemia induced by permanent occlusion of the middle cerebral artery, transcripts of protein inhibitor of neuronal nitric oxide synthase progressively accumulated in cortical neurons bordering the infarct area. After transient middle cerebral artery occlusion however, messenger RNA levels of protein inhibitor of neuronal nitric oxide synthase increased in the reperfused neocortex. Our findings indicate that cerebral ischemia leads to an increase in neuronal expression of protein inhibitor of neuronal nitric oxide synthase in brain regions where sustained or “uncoupled” nitric oxide synthase activity may be detrimental to neurons. Lack of post-ischemic induction of protein inhibitor of neuronal nitric oxide synthase in CA1 pyramidal neurons may result in high nitric oxide synthase activity after global ischemia and could contribute to delayed neuronal cell death.

Published
1998
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18. Effect of global system for mobile communication (GSM) microwave exposure on blood-brain barrier permeability in rat

Author

K.-A. Hossmann, Klaus Fritze, Günter Mies, Christoph Wiessner, Bernd Schmitz, Clemens Sommer, and Marika Kiessling

Subjects
Male, Pathology, medicine.medical_specialty, Serum albumin, Blood–brain barrier, Pathology and Forensic Medicine, Capillary Permeability, Andrology, Cellular and Molecular Neuroscience, medicine, Animals, Irradiation, Rats, Wistar, Microwaves, Global system, biology, Chemistry, Immunohistochemistry, Extravasation, Rats, Telephone, Cold Temperature, Sarcoplasmic Reticulum, medicine.anatomical_structure, Blood-Brain Barrier, Permeability (electromagnetism), biology.protein, Neurology (clinical), Blood brain barrier permeability, Microwave
Abstract

We investigated the effects of global system for mobile communication (GSM) microwave exposure on the permeability of the blood-brain barrier using a calibrated microwave exposure system in the 900 MHz band. Rats were restrained in a carousel of circularly arranged plastic tubes and sham-exposed or microwave irradiated for a duration of 4 h at specific brain absorption rates (SAR) ranging from 0.3 to 7.5 W/kg. The extravasation of proteins was assessed either at the end of exposure or 7 days later in three to five coronal brain slices by immunohistochemical staining of serum albumin. As a positive control two rats were subjected to cold injury. In the brains of freely moving control rats (n = 20) only one spot of extravasated serum albumin could be detected in one animal. In the sham-exposed control group (n = 20) three animals exhibited a total of 4 extravasations. In animals irradiated for 4 h at SAR of 0.3, 1.5 and 7.5 W/kg (n = 20 in each group) five out of the ten animals of each group killed at the end of the exposure showed 7, 6 and 14 extravasations, respectively. In the ten animals of each group killed 7 days after exposure, the total number of extravasations was 2, 0 and 1, respectively. The increase in serum albumin extravasations after microwave exposure reached significance only in the group exposed to the highest SAR of 7.5 W/kg but not at the lower intensities. Histological injury was not observed in any of the examined brains. Compared to other pathological conditions with increased blood-brain barrier permeability such as cold injury, the here observed serum albumin extravasations are very modest and, moreover, reversible. Microwave exposure in the frequency and intensity range of mobile telephony is unlikely to produce pathologically significant changes of the blood-brain barrier permeability.

Published
1997
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19. Functional Activation of Cerebral Blood Flow after Cardiac Arrest in Rat

Author

K.-A. Hossmann, Bernd Schmitz, and Bernd W Böttiger

Subjects
Male, Resuscitation, Ischemia, Hemodynamics, Stimulation, Return of spontaneous circulation, Somatosensory system, Nervous System, 030218 nuclear medicine & medical imaging, Rats, Sprague-Dawley, 03 medical and health sciences, 0302 clinical medicine, Laser-Doppler Flowmetry, medicine, Animals, business.industry, Blood flow, Carbon Dioxide, medicine.disease, Heart Arrest, Rats, Electrophysiology, Neurology, Cerebral blood flow, Somatosensory evoked potential, Cerebrovascular Circulation, Anesthesia, Neurology (clinical), Cardiology and Cardiovascular Medicine, business, 030217 neurology & neurosurgery
Abstract

After a period of global cerebral ischemia, CO2 reactivity and the hemodynamic–metabolic activation to functional stimulation are transiently suppressed. This raises the question of whether the impaired functional coupling reflects disturbances of functional integrity of the brain or an impaired cerebrovascular reactivity. We, therefore, compared the recovery of CO2 reactivity with that of somatosensory evoked potentials, functional flow activation and neurologic deficits in a rodent model of cardiac arrest-induced cerebral ischemia, followed by up to 7 days of reperfusion. Cardiac arrest of 10 minutes' duration was produced in 24 animals by electrical fibrillation of the heart. Five animals were sham-operated controls. Resuscitation was performed by external cardiac massage, using standard resuscitation procedures. Functional activation was carried out under chloralose anesthesia by electrical stimulation of forepaws. CO2 reactivity was tested by ventilation of animals with 6% CO2. During functional and hypercapnic stimulation CBF was measured in the somatosensory cortex using laser–Doppler flowmetry, and at the end of the experiment by 14C-iodoantipyrine autoradiography. Neurologic deficits were scored by evaluating consciousness and various sensory and motor functions. In control animals 6% CO2 increased CBF measured by laser–Doppler flowmetry by 28.8% ± 8.7%. Forepaw stimulation generated somatosensory evoked potentials with an amplitude of 750 ± 217 μV and increased CBF measured by laser–Doppler flowmetry by 86.0% ± 18.1%. After return of spontaneous circulation, CO2 reactivity was transiently reduced to about 30% of control at 1 hour of reperfusion ( P < 0.05) but returned to near control at 5 hours. Somatosensory evoked potential amplitudes were reduced to 15% of control at 45 minutes of reperfusion and returned to only 50% to 60% at 3 and 7 days after return of spontaneous circulation ( P < 0.05). Functional activation of blood flow was completely suppressed during the first hour after return of spontaneous circulation but also recovered to 50% to 60% of control at 3 days after return of spontaneous circulation ( P < 0.05). Linear regression analysis revealed a significant correlation between recovery of functional activation of blood flow and both recovery of the amplitude of somatosensory evoked potentials ( P = 0.03) and the neurologic deficit score ( P = 0.02), but not between neurologic deficit score and recovery of CO2 reactivity or somatosensory evoked potential amplitudes. These data demonstrate that the suppression of functional activation of blood flow after 10 minutes cardiac arrest is not related to impairment of coupling mechanisms but reflects ongoing disturbances of the functional integrity of the brain. Assessment of functional flow coupling is a reliable way to study postischemic recovery of the brain.

Published
1997
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21. Effect of trophic factors on delayed neuronal death induced byin vitro ischemia in cultivated hippocampal and cortical neurons

Author

M. Kusumoto, K.-A. Hossmann, and E. Dux

Subjects
medicine.medical_specialty, Programmed cell death, Basic fibroblast growth factor, Ischemia, Biology, Hippocampal formation, medicine.disease, Biochemistry, Blood proteins, Cellular and Molecular Neuroscience, chemistry.chemical_compound, medicine.anatomical_structure, Endocrinology, chemistry, Neurotrophic factors, Cerebral cortex, Internal medicine, Immunology, medicine, Hippocampus (mythology), Neurology (clinical)
Abstract

The effect of trophic factors on neuronal survival after 30 min oxygen and glucose deprivation (in vitro ischemia) was studied in primary hippocampal and cortical neuronal cultures of rat. In vitro ischemia was produced at 37°C by placing cultures in glucose-free medium, the oxygen content of which was removed by gassing with pure argon. After in vitro ischemia neurons were allowed to recover either in serum-free minimal essential medium (MEM) or in MEM containing 5% native horse serum, 100 ng/ml basic fibroblast growth factor (bFGF) or 10 ng/ml transforming growth factor-β1 (TGF-β1), respectively. Cultures that recovered in serum-free medium suffered a progressive type of neuronal injury: survival of either cortical or hippocampal neurons declined from about 60% after 1 h to 50% after 3 h, 40% after 6 h and less than 20% after 24 h. Addition of serum proteins to the incubation medium did not influence early survival (up to 3-6 h) but significantly improved survival after 24 h (more than 40% in both hippocampal and cortical cultures). Addition of TGF-β1 and bFGF had only minor effects. These data show that serum reduces delayed ischemic cell death by a mechanism which is different from that of TGF-β1 or bFGF protection.

Published
1997
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22. Status of the neonatal rat brain after NMDA-induced excitotoxic injury as measured by MRI, MRS and metabolic imaging

Author

Dieter Leibfritz, K.-A. Hossmann, M. van Lookeren Campagne, Wolfgang Dreher, C. A. F. Tulleken, A. van der Toorn, M. Hoehn-Berlage, Klaas Nicolay, H. B. Verheul, Rick M. Dijkhuizen, Thoralf Niendorf, and Mechanical Engineering

Subjects
Neonatal rat, medicine.medical_specialty, Metabolic imaging, Excitotoxicity, Metabolism, Biology, medicine.disease_cause, Endocrinology, Nuclear magnetic resonance, In vivo, Internal medicine, medicine, Molecular Medicine, NMDA receptor, Effective diffusion coefficient, Radiology, Nuclear Medicine and imaging, medicine.symptom, Spectroscopy, Acidosis
Abstract

Intrastriatal injection of the excitotoxin N-methyl-dsc-aspartate (NMDA) in neonatal rat brain resulted in an acute ipsilateral decrease of the apparent diffusion coefficient (ADC) of brain tissue water, as measured with diffusion-weighted MRI. The early diffusion changes were accompanied by only mild changes in the overall metabolic status as measured by in vivo1H MRS and 31P MRS and metabolic imaging of brain sections. Minimal decreases in the high-energy phosphate levels and a small hemispheric acidosis were observed in the first 6¿h after NMDA administration. In addition, there was very modest lactate accumulation. Twenty-four hours after the induction of the excitotoxic injury the tissue energy status was still only moderately affected, whereas an overall decrease of 1H MRS-detected brain metabolites was found. Treatment with the non-competitive NMDA-antagonist MK-801 given within 90 min after NMDA injection rapidly reversed the NMDA-induced changes in the entire ipsilateral hemisphere. The effect of the competitive NMDA-antagonist D-CPPene was restricted to the cortical areas and was accomplished on a slower time scale. Our results indicate that; (i) early excitotoxicity in the neonatal rat brain does not lead to profound changes in the metabolic status; and (ii) brain tissue water ADC changes are not necessarily associated with a metabolic energy failure.

Published
1996

23. Glial Expression of the β-Amyloid Precursor Protein (APP) in Global Ischemia

Author

K.-A. Hossmann, Richard B. Banati, Georg W. Kreutzberg, Jochen Gehrmann, and C. Wießner

Subjects
Male, Pathology, medicine.medical_specialty, Necrosis, Ischemia, Fluorescent Antibody Technique, Hippocampus, Biology, Amyloid beta-Protein Precursor, Parietal Lobe, Glial Fibrillary Acidic Protein, mental disorders, medicine, Animals, Rats, Wistar, Microglia, Glial fibrillary acidic protein, Neurodegeneration, Brain, medicine.disease, Immunohistochemistry, Corpus Striatum, Rats, medicine.anatomical_structure, nervous system, Neurology, Ischemic Attack, Transient, Astrocytes, Peripheral nerve injury, biology.protein, Neuroglia, Neurology (clinical), medicine.symptom, Cardiology and Cardiovascular Medicine
Abstract

The β-amyloid precursor protein (APP) bears characteristics of an acute-phase protein and therefore is likely to be involved in the glial response to brain injury. In the brain, APP is rapidly synthesized by activated glial cells in response to comparatively mild neuronal lesions, e.g., a remote peripheral nerve injury. Perfusion deficits in the brain result largely in neuronal necrosis and are a common condition in elderly patients. This neuronal necrosis is accompanied by a pronounced reaction of astrocytes and microglia, which can also be observed in animal models. We have therefore studied in the rat, immunocytochemically, the induction of APP after 30 min of global ischemia caused by four-vessel occlusion. The postishemic brain injuries were examined at survival times from 12 h to 7 days. From day 3 onward, APP immunoreactivity was strongly induced in the CA1and CA4regions of the rat dorsal hippocampus as well as in the dorsolateral striatum. In these areas, the majority of APP-immunoreactive cells were reactive glial fibrillary acidic protein (GFAP)-positive astrocytes, as shown by double-immunofluorescence labeling for GFAP and APP. Additionally, small ramified cells, most likely activated microglia, expressed APP immunoreactivity. In contrast, in the parietal cortex, APP immunoreactivity occurred focally in clusters of activated microglia rather than in astrocytes, as demonstrated by double-immunofluorescence labeling for APP and the microglia-binding lectin Griffonia simplicifolia isolectin B4. In conclusion, following global ischemia, APP is induced in reactive glial cells with spatial differences in the distribution pattern of APP induction in astrocytes and microglia.

Published
1995
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24. Biochemical changes and gene expression following traumatic brain injury: Role of spreading depression

Author

D M, Hermann, G, Mies, and K A, Hossmann

Abstract

The effects of spreading depression-like DC depolarizations on biochemical changes and gene expression were examined following trau-matic neocortical lesions, as induced by transcranial cold injury. The surrounding of traumatic cold lesions was characterized by increased glu-cose and lactate contents, without major disturbances of protein synthesis or energy state. A transient pH decrease by 0.4 units was noticed 1 h post-injury, which shifted towards alkaline values by 3 h. These changes were similar in animals with spontaneous spreading depression-like DC shifts (n = 14) and those without spreading depressions (n = 7), but there was a marked difference in the gene response. In injured animals without SD, only a short-lasting response of c-fos, junB, c-jun and MKP-1 mRNAs as well as c-Fos protein was bilaterally found in the piri-form cortex, and - with ipsilateral dominance - the dentate gyrus and hippocampal CA3/4 fields at 1 h after lesioning. In injure d animals with spreading depressions, on the contrary, a strong elevation was seen in layers II-IV and VI of the injury-remote ipsilateral cerebral cortex, which persisted over as long as 6 h. The expression of c-fos, junB and MKP-1 mRNAs was closely related to the time interval between the last spreading depression and the end of the experiments. Levels were highest shortly after transient DC shifts, and decreased thereafter mono-exponentially with half-lives of 48, 75 and 58 min for c-fos, junB and MKP-1 mRNAs, respectively. Thus, spreading depression is a prominent factor influencing the trauma-related gene response, but - in contrast to focal ischemia - it does not aggravate the metabolic dysfunction.

Published
2012

25. Effect of serum on intracellular calcium homeostasis and survival of primary cortical and hippocampal CA1 neurons following brief glutamate treatment

Author

K.-A. Hossmann, E. Dux, and Akira Uto

Subjects
medicine.medical_specialty, Cell Survival, Basic fibroblast growth factor, Glutamic Acid, Hippocampus, chemistry.chemical_element, Calcium, Biology, Biochemistry, Calcium in biology, Cellular and Molecular Neuroscience, chemistry.chemical_compound, Lactate dehydrogenase, Internal medicine, medicine, Animals, Horses, Rats, Wistar, Cells, Cultured, Neurons, Cell Death, L-Lactate Dehydrogenase, Glutamate receptor, Neurotoxicity, Blood Proteins, medicine.disease, Rats, Blood, Endocrinology, medicine.anatomical_structure, chemistry, Cerebral cortex, Nerve Degeneration, Immunology, Neurology (clinical)
Abstract

Glutamate neurotoxicity was studied in primary neuronal cultures prepared from rat cerebral cortex and hippocampal CA1 sector. Neurons were cultivated with 5% native horse serum and then exposed to 0.1 or 1.0 mM glutamate for 5 min. Subsequently, neurons were allowed to recover for 24 hours either in the presence or in the absence of 5% native horse serum. In the absence of serum, neurons showed morphological signs of degeneration and exhibited marked loss of vitality as tested by vital staining and release of lactate dehydrogenase (LDH). In contrast, when neurons were cultivated in the presence of serum, no degenerative changes were seen and the neurons survived. Heat inactivated serum did not prevent neuronal death but addition of basic fibroblast growth factor (bFGF) or transforming growth factor-beta 1 (TGF-beta 1) had the same protective effect as native serum. Measurements of intracellular calcium activity ([Ca2+]i) with the indicator dye fura-2 revealed a sharp increase during glutamate exposure. In the absence of serum, [Ca2+]i returned to near control within 5 min but it secondarily increased after 1 hour to almost the same level as during glutamate exposure. This delayed increase was more pronounced in CA1 than in cortical neurons, it correlated linearly with the initial rise during glutamate exposure, and it was greatly reduced in the presence of serum. These observations suggest that glutamate neurotoxicity in vitro is a function of the delayed and not of the primary rise of intracellular calcium activity, and that trophic factors prevent neurotoxicity by attenuating this delayed response.

Published
1994
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26. Fourth meeting of the European Neurological Society 25–29 June 1994 Barcelona, Spain

Author

H. Hattig, C. Delli Pizzi, M. C. Addonizio, Michelle Davis, A. R. Giovagnoli, L. Florensa, M. Roth, J. de Kruijk, Francisco Lacruz, Ph. Dewailly, A. Toygar, C. Avendano, P.P. De Deyn, J. F. Hurtevent, F. Lomeila, T. W. Wong, Gordon T. Plant, M. Bud, H. J. Willison, DH Miller, D. W. Langdon, R. Cioni, J. Servan, A. Kaygisiz, E. Racadot, D. B. Schens, E. Picciola, L. Falip, C. Bouchard, J. Jotova, A. Jorge-Santamaria, P. Misra, A. Dufour, C. P. Panagopoulos, A. Venneri, B. Sredni, B. Angelard, M. Janelidze, M. Carreno, J. Obenberger, J. Pouget, H. W. Moser, R. Kaufmann, J. A. Molina, D. Linden, A. Martin Urda, E. Uvestad, A. Krone, J. P. Cochin, J. Mallecourt, A. Cambon-Thomsen, K. Violleau, P. Osschmann, A. M. Durocher, E. Bussaglia, D. M. Danielle, H. Efendi, C. Van Broeckhoven, K. G. Jordan, W. Rautenberg, C. Iniguez, J. M. Delgado, Graham Watson, M. Lawden, Gareth J. Barker, K. Stiasny, James T. Becker, G. Campanella, E. Peghi, A. Poli, A. Haddad, T. Yamawaki, Giacomo P. Comi, S. Sotgiu, B. Ersmark, A. Pomes, M. Ziegler, P. Ferrante, P. Ruppi, H. KuÇukoglu, R. Bouton, U. K. Rinne, P. Vieregge, M. Dary, P. Giunti, Peter J. Goadsby, S. Jung, E. Secor, A. Steinberg, N. Vila, M. A. Hernandez, M. Cursi, A. Enqelhardt, A. Engelhardt, J. Veitch, F. Di Silverio, F. Arnaud, B. Neundörfer, R. Brucher, Dominique Caparros-Lefebvre, B. Meyer, Marianne Dieterich, M. H. Snidaro, R. Gomez, R. Cerbo, M. Ragno, J. M. Vance, S. Nemni, A. Caliskan, F. Barros, I. Velcheva, D. Ceballos-Baumann, V. Barak, A. Avila, N. Antonova, F. Resche, S. Pappata, L. Varela, S. R. Silveira Santos, A. Cammarota, L. Naccache, Y. Nara, E. Tournier-Lasserves, R. Mobner, T. Chase, A. Ensenyat, J. Ulrich, G. Giegerich, M. Rother, M. Revilla, N. Nitschke, K. Honczarenko, E. Basart Tarrats, J. Blin, B. Jacob, J. Santamaria, S. Knezevic, J. L. Castillo, M. Antem, J. Colomer, O. Busse, Didier Hannequin, S. Carrier, J. B. Ruidavets, C. Rozman, J. Bogoussslavsky, J. Pascual Calvet, E. Monros, J. M. Polo, M. Zucconl, Javier Muruzabal, R. R. Allen, R. Rivolta, K. Haugaard, A. Nespolo, K. Hoang-Xuang, G. Bussone, T. Avramidis, E. Corsini, Christiana Franke, T. Vinogradova, H. Boot, K. Vestergaard, G. H. Jansen, N. Argentino, M. Raltzig, W. Linssen, Mark B. Pepys, P. Roblot, L. Lauritzen, E. Fainardi, D. Morin, T. X. Arbizu Urdiain, J. Wollenhaupt, S. Bostantjopoulou, G. Pavesi, A. D. Forman, Giovanni Fabbrini, D. Jean, J. J. Archelos, M. I. Blanchs, M. Del Gobbo, Anna Carla Turconi, Ch. Derouesné, Elio Scarpini, A. Visbeck, P. Castejon, J. P. Renou, F. Mounier-Vehier, G. Potagas, Ch. Duyckaerts, A. Filla, R. Schneider, G. Ronen, K. Nagata, J. P. Vedel, A. Henneberg, G. van Melle, C. Baratti, H. Knott, M. C. Prevett, A. Bes, B. Metin, Jos V. Reempts, L. Martorell, Mefkure Eraksoy, H. O. Handwerker, D. S. Younger, O. Oktem, D. Frongillo, C. Soriano-Soriano, L. Niehaus, F. Zipp, A. Tartaro, S Newman, R. H. Browne, P. Davous, R. Sanchez, M. Muros, M. E. Kornhuber, A. Lavarone, M. Mohr, M. R. Garcia, S. Russell, H. Kellar-Wood, M. R. Tola, B. Ostermeyer, Ch. Tzekov, K. Sartor, E. B. Ringelstein, P. P. Gazzaniga, Paul Krack, H. Fidaner, H. Rico, T. Dbaiss, F. Alameda, E. Torchiana, L. Rumbach, I. Charques, J. M. Bogaard, C. D. Frith, L. J. Rappelle, R. Brenner, A. Joutel, K. Fuxe, G. HÄcker, M. J. Blaser, J. Valls-SolÇ, G. Ulm, M. Alberdi, A. Bock, F. W. Bertelsmann, U. Wieshmann, J. Visa, J. R. Lupski, D. D'Amico, L. M. P. Ramos, A. A. Vanderbark, R. Horn, M. Warmuth, Dietmar Kühne, Mark S. Palmer, C. Ehrenheim, E. Canga, S. Viola, O. Scarpino, P. Naldi, R. Almeida, A. A. Raymond, J. Gamez, Stephan Arnold, A. DiGiovanni, J. Dalmau, C. C. Chari, H. F. Beer, J. C. Koetsier, J. Iriarte, E. Yunis, J. Casadevall, E. Le Guern, E. Stenager, S. R. Benbadis, J. M. Warter, F. Burklin, I. Theodorou, L. Johannesen, G. A. Graveland, X. Leclerc, I. Vecchio, L. Ozelius, G. Nicoletti, R. K. Gherardi, E. Esperet, M. L. Delodovici, F. Cattin, F. Paiau, Giorgio Sacilotto, C. A. J. Broere, D. Chavdarov, J. P. Willmer, C. H. Hawkes, Th. Naegele, E. Ellie, E. Dartigues, M. J. Guardiola, S. Hesse, Z. Levic, Marco Rovaris, P. Saugeir-Veber, B. A. Yaqub, H. F. Durwen, R. Larumbe, J. Ballabrina, M. Sendtner, J. Röther, M. Horstink, C. Kluglein, M.P. Montesi, H. Apaydin, J. Montoya, E. Waubant, Ch. Verellen-Dunoulin, A. Nicolai, J. Lopez-Delval, R. Lemon, G. Cantinho, E. Granieri, A. Zeviani, Wolfgang H. Oertel, U. Ficola, V. Di Piero, V. Fragola, K. Sabev, M. V. Guitera, I. Turki, F. Bolgert, P. Ingrand, J. M. Gobernado, L. M. E. Grimaldi, S. Baybas, B. Eymard, Y. Rolland, Y. Robitaille, Ta. Pampols, P. J. Koehler, A. Carroacedo, J. Vilchez, S. Di Vittorio, I. R. Rise, T. Nagy, M. Kuffner, E. Palazzini, A. Ott, J. Pruim, T. X. Arbizu, E. Manetti, C. Cervera, S. Felber, G. Gursoy, J. Scholz, G. A. Buscaino, M. S. Chen, A. Pascual, J. Hazan, J. U. Gajda, J. G. Cea, G. Bottini, G. Damalik, F. Le Doze, G. Bonaldi, J. M. Hew, C. Messina, A. M. Kennedy, J. M. Carney, N. M. F. Murray, M. Parent, M. Koepp, V. Dimova, D. De Leo, K. Jellinger, G. Salemi, S. Mientus, M. L. Hansen, F. Mazzucchelli, J. Vieth, M. Mauri, E. Bartels, L. Johannsen, C. Humphreys, J. Emile, D. N. Landon, E. Kansu, R. Sanchez-Pernaute, Rsj Frackowiak, M. Gonzalez Torres, L. Oller, C. Machedo, J. Kother, M. Billiard, H. Durak, T. Schindler, A. Frank, A. Uncini, A. Sbriccoli, C. Farinas, D. W. Paty, N. Fast, A. T. Zangaladze, A. Kerkhofs, J. M. Pino Garcia, I. De la Fuente, B. Marini, L. Gomez, I. Rubio, Alessandra Bardoni, C. Brodie, P. Acin, U. Sliwka, S. A. Hawkins, S. Tardieu, F. Vitullo, J. M. Pereira Monteino, R. Gagliardi, T. Jezewski, A. Cano, T. Lempert, F. Abad Alegria, G. Rotondo, D. Ince, C. Martinez Parra, Y. Huang, H. Luders, Y. Steinvil, F. G. A. Van Der Meche, R. Bianchi, A. Sanchez, T. Sevilla, J. M. Ketelslegers, A. Domzal-Stryga, M. Pandolfo, M. O. Josse, K. W. Neff, I. Blanco, G. W. Bruyn, O. W. Witte, J. L. Thibault, G. Andersen, J. Pariset, A. Marcone, R. J. M. Lane, A. Hofman, M. Verin, T. Matilla, P. Bedoucha, J. Roche, M. Lai, M. Collard, A. Ugarte, F. Gallecho, D. Silbersweig, C. Kennard, J. P. Azulay, T. W. Ho, P. L. I. Dellemijn, R. Girardello, F. Baas, B. Voss, F. Rozenberg, E. M. Brocker, V. Stanev, A. A. J. Soeterboek, A. Marra, A. Rey, E. Ertem, M. Sawradewicz-Rybak, J. De Keyser, P. Cavallari, F. Proust, Y. Chevalier, H. C. Hansen, D. Leys, C. A. Davie, K. Hoang-Xuan, C. Bairati, H. van Crevel, Thomas T. Warner, B. Bompais, A. Dobbeleir, T Campbell, C. Macko, C. J. M. Klijn, M. Dussallant, T. P. Berlit, W. Rozenbaum, M. J. van den Bent, W. A. Rocca, M. Muller, H. Hundemer, U. Zifko, M. Campera, F. Drislane, D. Ranoux, T. M. Kloss, Anil Kumar, I. Ruolt, C. Bargnani, B. Marescau, N. A. Losseff, S. Notermans, B. Kint, E. T. Burke, C. Aykut, J. Matias Guiu, P. Maquet, T. Drogendijk, M. Leone, K. von Ammon, M. Pepeliarska, C. Prados, L. DiGiamberardino, T. Logtenberg, G. Lenoir, I. Castaldo, Damhaut, M. Radionova, G. Sirabian, R. Navon, Giovanni Antonini, K. Al Moutaery, E. Chamas, R. Schönhuber, M. Giannini, B. Debilly, I. Labatut, H. Henon, J. A. Egido, M. Baudrimont, J. N. Lorenzo, J. E. C. Bromberg, R. Antonacci, J. J. Vilchez, T. Moulin, B. Rautenstrauss, Giovanni Meola, J. Noth, S Mammi, P. Laforet, F. Lopez, C. Gehring, S. Bort, G. Rancurel, D. Decamps, S. Kostadinova, Y. Shapira, B. Neundoerfer, D. Chavrot, M. Solimena, J. P. Salier, W. Deberdt, R. Hoff-Jörgensen, A. Messina, S. Meairs, G. Rosoklija, E. Nelis, I. Bertran, C. Ertekin, J. Lohmeyer, Mitermayer Galvao dos Reis, L. Calo, E. Maccagnano, A. P. Hays, J. Verlooy, M. G. Forno, T. Blanco, L. Bail, Gabriella Silvestri, J. Montero, F. Bertrand, R. T. Ghnassia, C. Besses, T. Sereghy, F. Shalit, G. Bogliun, S. Braghi, St. Baykouchev, C. Franke, A. Lasa, L. C. Archard, J. Kriebel, S. Shaunak, M. Nocito, Alexander Tsiskaridze, E. Manfredini, T. Seigal, David G. Gadian, M. Barlas, J. D. Degos, C. Seeber, J. Caemert, J. L. Mas, R. B. Pepinsky, M. G. D'Angelo, N. Baumann, S. Yorifuji, H. P. Endtz, M. A. Cassatella, R. A. C. Hughes, V. Golzi, A. Bittencourt, A. Ferreira, M. Sanson, C. Alper, M. Vermeulen, M. A. A. van Walderveen, E. Alexiou, C. H. Lucas, M. Fiorelli, Y. N. Debbink, R. Gil, S. Congia, T. Banerjee, J. M. Bouchard, A. N. Pinto, A. Ceballos-Baumann, G. Grollier, P. I. M. Schmitz, M. D. Catata, N. Lahat, N. S. Rao, P. Papathanasopoulos, J. Valls-Solé, D. Claus, G. Schroter, A. Castro, C. Videbaek, R. Martinez Dreke, A. D. Platts, M. Hermesl, A. C. PeÇanha-Martins, M. Cardoso Silva, P. Masnou, M. J. A. Tanner, Ch. Confavreux, B. Mishu, H. Rasmussen, L. Valenciano, Carlo Pozzilli, S. W. Li, V. Salzman, Y. Vashtang, Massimo Franceschi, M. Severo, G. Deuschl, S. Setien, G. Mariani, A. Protti, J. Castillo, M. J. B. Taphoorn, M. Frontali, I. Milonas, D. Decoq, J. A. Navarro, S. Castellvi-Pel, C. Ertikin, M. Urtasun, Y. Lajat, B. E. Kendall, E. Verdu, B. Gueguen, E. Boisen, R. Couderc, A Danek, JM Stevens, F. Nicoli, L. Feltri, M. L. Vazquez-Andre, J. A. Morgan-Hughes, L. D'Angelo, F. Y. Liew, L. F. Pascual, J. Patrignani Ochoa, Vittorio Martinelli, J. Cophignon, L. Zhang, S. Martin, J. F. Meder, H. C. Buschmann, L. Bertin, J. van Gijn, A. Barreiro, A. Cools, C. Leon, A. Berod, E. A. Anllo, E. Zanette, L. Petrov, R. Barona, B. Gallicchio, P. J. Cozzone, N. Diederich, G. Cancel, L. Schelosky, P. Orizaola, K. Yulug, S. Ozer, Valeria A. Sansone, B. Guiraud-Chaumeil, K. Voigt, P. Labauge, M. Eoli, J. Zhu, J. Aguirre, M. Ferrarini, B. Zyluk, E. Planas, A. Cadilha, C. Tortorella, H. Bismuth, C. E. Counsell, A. Laun, A. Ferlini, Rio J. Montalban, N. Biary, L. Becker, M. Fardeau, M. Poloni, V. M. S. de Bruin, C. Fornada, J. Barros, E. Ganzmann, E. Touze, D. Wallach, J. Peila, H. Fujimura, M. T. Iba-Zizen, G. Macchi, C. Villoslada, R. Gouider, Ph. Rondepierre, P. Grummich, P. Chiodi, C. Conte, M. Michels, P. Annunziata, G. Semana, C. Sommer, J. Vajsar, D. Zekin, J. Kulisevsky, David G. Munoz, B. Jacotot, M. Magoni, A. Luxen, T. Garcia-Silva, S. Di Cesare, Christophe Tzourio, M. Gomori, I. Picomell, L. Santoro, F. Villa, Giovanni Pennisi, T. Ribalta, J. M. Molto, L. Marzorati, P. Loiseau, F. Gemignani, A. Gironell, J. Wissel, A. Prusinski, F. Cailloux, P. Villanueva-Hemandez, P. Cozzone, T. Del Ser, J. Sans-Sabrafen, M. Zappia, P. W. A. Willems, G. Tchernia, D. Gardeur, R. Bauer, F. Palomo, H. Metz, S. Lamoureux, C. Chastang, I. Reinhard, A. Goldfarb, S. Harder, Jordi Río, C. Ozkara, E. Tekinsoy, P. Vontobell, J. De Recondo, M. Rabasa, L. Lacomblez, F. Boon, Dgt Thomas, V. Palma, Renato Mantegazza, A. Dervis, M. Nueckel, B. YalÇinerner, I. Duran, G. Dalla Volta, A. Zubimendi, J. Pinheiro, A. Marbini, Xavier Montalban, H. Wekerle, X. Pereira Monteino, F. Crespo, F. Koskas, N. Battistini, C. Ruiz, H. Offner, J. de Pommery, P. Kanovsky, J. Y. Barnett, J. Pardo, G. Tomei, R. Rene, H. M. Lokhorst, P. Thajeb, H. Bilgin, D. McGehee, R. Fahsold, L. Morgante, Katie Sidle, C. Delwaide, M. N. Diaye, P. H. Rice, A. Creange, C. Sabev, K. Stephan, K. WeilBenborn, G. Magnani, L. Grymonprez, F. Cardellach, M. Kaps, N. G. Meco, F. Vega, V. Bonifati, A. Desomer, M. Baldy-Moulinier, G. Kvale, F. J. Authier, B. Yegen, T. Ho, J. M. Rozet, E. A. Cabanis, L. Bruce, L. Ambrosoli, M. A. Petrella, M. Hernandez, P. Timmings, H. B. van der Worp, F. Mahieux, A. Urbano-Marquez, D. A. Krendel, A. A. Garcia, R. Divari, R. Michalowicz, M. R. Piedmonte, M. Bondavalli, M. Zanca, P. F. Ippel, Onofre Combarros, B. Tavitian, E. Hirsch, I. Anastasopoulos, A. Roses, A. Köhler, P. Vienna, V. Timmerman, P. Sergi, F. Cornelio, A. Di Pasquale, R. Verleger, S. Castellvirel, J. Proano, B. van Moll, F. Rubio, W. Hacke, I. Lavenu, L. Zetta, M. W. Tas, N. Bittmann, M. Bonamini, O. R. Hommes, V. Dousset, N. Afsar, S. Belal, R. R. Myers, J. Goes, Giuseppe Vita, E. Clementi, V. G. Karepov, M. Jueptner, A Vincent, P. Emmrich, Th. Heb, A. Caballo, J. Gallego, T. Mokrusch, C. Perla, L. Gebuhrer, O. Titlbach, Alessandro Prelle, A. Czlonkowska, M. Russo, D. Hadjiev, T. S. Chkhikvishvili, M. Oehlschlager, G. Becker, I. Günther, E. N. Stenager, J. Garcia Agundez, J. Casademont, J. Batlle, S. Podobnik-Sarkanji, C. Alonso-Villaverde, B. Delaguillaume, B. Genc, B. Mazoyer, A. Rodriguez-Al-barino, Ch. Hilger, B. Ferrero, R. Price, W. Grisold, L. Fuhry, D. Oulbani, D. Ewing, A. Petkov, W. Walther, A. Gokyigit, John Newsom-Davis, J. Tayot, D. Seliak, G. Pelliccioni, D. Campagne, K. Kessler, F. Boureau, D. Perani, J. P. N'Guyen, N. Tchalucova, B. A. Antin-Ozerkis, C. Lacroix, B. D. Aronovich, I. H. Jenkins, E. A. dos Reis, M. Hortells, H. M. Meinck, H. Ch. Buschmann, S. C. J. M. Jacobs, T. Wetter, P. Creissard, N. Martinez, J. Weidenfeldl, H. J. Sturenburg, G. Damlacik, V. Gracia, J. C. Turpin, A. Pou-Serradell, J. P. Vincent, T. Gagoshidze, U. Ozkutlu, M. McLeod, K. Siegfried, I. Tchaoussoglou, J. Hildebrand, S. Kowalska, M. C. Picot, G. Galardin, L. Crevits, F. Andreetta, S. 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Subjects
Neurology, business.industry, Media studies, Library science, Medicine, Neurology (clinical), business
Published
1994
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27. Differential Expression of the Immediate Early Genes c-Fos, c-Jun, JunB, and NGFI-B in the Rat Brain following Transient Forebrain Ischemia

Author

K.-A. Hossmann, Peter Vogel, Back T, Neumann-Haefelin T, and Christoph Wiessner

Subjects
Male, Pathology, medicine.medical_specialty, JUNB, Ischemia, Gene Expression, Hippocampus, In situ hybridization, Striatum, c-Fos, Genes, jun, medicine, Animals, Tissue Distribution, RNA, Messenger, Rats, Wistar, Genes, Immediate-Early, In Situ Hybridization, Neocortex, biology, c-jun, Brain, Genes, fos, medicine.disease, Immunohistochemistry, Molecular biology, Rats, medicine.anatomical_structure, Neurology, Ischemic Attack, Transient, biology.protein, Neurology (clinical), Cardiology and Cardiovascular Medicine, Proto-Oncogene Proteins c-fos
Abstract

The temporospatial expression pattern of four immediate early genes (IEGs) (c- fos, c- jun, junB, NGFI-B) following 30 min of global ischemia was investigated in rat brains by in situ hybridization and immunohistochemistry (c- fos). All examined IEG mRNAs, as well as Fos-like immunoreactivity, increased transiently in vulnerable and resistant brain regions following ischemia, but the induction profiles were distinct. Ischemia caused a post-ischemic early-onset, transient c- fos induction in widespread regions, as well as a late-onset induction restricted to vulnerable regions. Late-onset c- fos induction was observed in the CA1 region and the ventral thalamus but not in the striatum or neocortex, where neurons degenerate at a quicker pace. After recirculation, c- jun mRNA appeared to be initially coinduced with c- fos mRNA, but c- jun mRNA levels remained elevated or increased in various regions, including all vulnerable regions, when c- fos mRNA had already declined to near basal levels. Compared to c- fos and c- jun, junB induction was less pronounced and confined largely to the dentate gyrus. NGFI-B mRNA increased moderately and only in brain regions exhibiting the most dramatic c- fos increases and with similar kinetics. The differential activation of the investigated IEGs suggests that rather complex long-term adaptive processes may be initiated at the genomic level after global ischemia. The present findings provide further evidence that the activation of IEGs forms part of the brain's metabolic response to ischemia, but no simple correlation appears to exist between the induction of the investigated IEGs and the phenomenon of selective vulnerability.

Published
1994
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28. Cortical Negative DC Deflections following Middle Cerebral Artery Occlusion and KCl-Induced Spreading Depression: Effect on Blood Flow, Tissue Oxygenation, and Electroencephalogram

Author

K.-A. Hossmann, Tobias Back, and K. Kohno

Subjects
Male, Partial Pressure, Ischemia, Arterial Occlusive Diseases, Potassium Chloride, medicine.artery, Occlusion, medicine, Animals, Rats, Wistar, Cerebral Cortex, Chemistry, Cortical Spreading Depression, Electric Conductivity, Electroencephalography, Blood flow, medicine.disease, Rats, Oxygen, Cerebrovascular Disorders, Electrophysiology, medicine.anatomical_structure, Neurology, Cerebral blood flow, Cerebral cortex, Cerebrovascular Circulation, Anesthesia, Cortical spreading depression, Middle cerebral artery, Neurology (clinical), Cardiology and Cardiovascular Medicine
Abstract

In the periphery of ischemic brain lesions, transient spreading depression-like direct current (DC) deflections occur that may be of pathophysiological importance for determining the volume of the ischemic infarct. The effect of these deflections on cerebral blood flow, tissue oxygen tension, and electrophysiology was studied in rats submitted to intraluminal thread occlusion of the middle cerebral artery (MCA) and compared with the changes following potassium chloride (KCl)-induced spreading depression of intact animals. Immediately after MCA occlusion, cortical laser–Doppler flow (LDF) in the periphery of the MCA territory sharply decreased to 35 ± 14% of control (mean ± SD; p < 0.05), tissue Po2 declined from 28 ± 4 to 21 ± 3 mm Hg (p < 0.05), and EEG power fell to ∼80% of control. During 7-h occlusion, 3–11 DC deflections with a mean duration of 5.2 ± 4.8 min occurred at irregular intervals, and EEG power gradually declined to 66 ± 16% of control (p < 0.05). During the passage of DC deflections, LDF did not change, but Po2 further declined to 19 ± 4 mm Hg (p < 0.05). KCl-induced depolarizations of intact rats were significantly shorter (1.4 ± 0.5 min; p < 0.05) and were accompanied by a 43% increase in LDF (p < 0.05) and a slight but significant increase in tissue Po2 from 22 ± 4 to 25 ± 4 mm Hg (p < 0.05). The comparison of periinfarct and KCl-induced depolarizations demonstrates that oxygen requirements are not coupled to an appropriate flow response in the periinfarct zone with severely reduced blood flow. The resulting episodes of relative hypoxia could explain the previously documented relationship between the number of depolarizations and infarct volume.

Published
1994
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29. MK-801, a glutamate antagonist, lowers flow threshold for inhibition of protein synthesis after middle cerebral artery occlusion of rat

Author

K.-A. Hossmann, Günter Mies, and K. Kohno

Subjects
Male, medicine.medical_specialty, Ischemia, Differential Threshold, Glutamic Acid, Hemodynamics, Brain Ischemia, Adenosine Triphosphate, Leucine, Internal medicine, medicine, Animals, Chemistry, General Neuroscience, Glutamate receptor, Antagonist, Proteins, Rats, Inbred Strains, Blood flow, Cerebral Arteries, medicine.disease, Constriction, Rats, Dizocilpine, Endocrinology, Cerebrovascular Circulation, Anesthesia, Autoradiography, NMDA receptor, Dizocilpine Maleate, Excitatory Amino Acid Antagonists, Perfusion, medicine.drug
Abstract

The effect of the glutamate antagonist MK-801 on the ischemic threshold of energy metabolism and protein synthesis (CPS) was studied in rats submitted to 3 h occlusion of the left middle cerebral artery (MCA). Local blood flow and CPS were measured by double tracer autoradiography, and local ATP content by bioluminescence imaging. In untreated animals breakdown of energy metabolism occurred at flow values below 15 +/- 1 and CPS inhibition below 51 +/- 15 ml/100 g/min (means +/- S.D.). MK-801 treatment (3 mg/kg immediately after MCA occlusion) did not change the ischemic flow threshold of energy failure (16 +/- 3 ml/100 g/min) but lead to a highly significant decline of the perfusion threshold for the inhibition of CPS to 19 +/- 4 ml/100 g/min (P0.01). Our data demonstrate that MK-801 dramatically reduces the threshold for the suppression of protein synthesis which could explain previously reported therapeutical effects on the reduction of brain infarct size.

Published
1993
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30. Simultaneous31P NMR spectroscopy and laser doppler flowmetry of rat brain during global ischemia and reperfusion

Author

K.-A. Hossmann, O. Kloiber, T. Miyazawa, and Mathias Hoehn-Berlage

Subjects
Male, medicine.medical_specialty, Pathology, Magnetic Resonance Spectroscopy, Intracellular pH, Ischemia, Hemodynamics, Brain Ischemia, Phosphocreatine, chemistry.chemical_compound, Internal medicine, Laser-Doppler Flowmetry, medicine, Animals, Radiology, Nuclear Medicine and imaging, Rats, Wistar, Spectroscopy, Acidosis, business.industry, Brain, Electroencephalography, Phosphorus, Blood flow, Laser Doppler velocimetry, medicine.disease, Rats, Endocrinology, chemistry, Cerebrovascular Circulation, Reperfusion, Molecular Medicine, medicine.symptom, Energy Metabolism, business, Perfusion
Abstract

The relationship between blood flow and metabolism was studied in halothane-anaesthetized, normothermic rats submitted to 30 min global ischemia by four-vessel occlusion. Phosphocreatine (PCr), ATP, intracellular pH and intracellular magnesium (pMg) were measured by "P NMR spectroscopy, and blood flow by laser Doppler flowmetry. Prior to ischemia the PCr/ATP ratio of fully relaxed spectra was 2.4 k 0.3, intracellular pH was 7.26 +_ 0.15 and pMg was 3.26 f 0.13. Vascular occlusion led to complete cessation of blood flow in four out of eight rats, and to incomplete ischaemia (< 10% of control) in the other four animals. During vascular occlusion EEG Battened and energy metabolism broke down in all but one animal with a residual blood flow of 8% of control. pH declined to 6.70 f 0.08. The speed of electrophysiological and metabolic recovery after 30 min ischemia varied considerably from animal to animal. Variability depended mainly on the recirculation delay (i.e., the interval from vascular release to normalization of blood flow) but was independent of residual blood flow during ischemia, pre-ischemic glucose, ischemic or post-ischemic acidosis, or the degree of post-ischemic hypoperfusion. After 3 h recirculation PCr and intracellular pH returned to normal but pMg was slightly increased, and ATP was reduced by up to 50% in all animals except the rat with incomplete breakdown of energy metabolism during ischemia. The dissociation between PCr and ATP is attributed to a loss of total adenylate, the severity of which depends on the quality of post-ischemic recirculation. The data refute the hypothesis that the quality of post-ischemic metabolic recovery depends mainly on the severity of tissue acidosis but stress the importance of post-ischemic haemodynamic factors for the speed and quality of brain resuscitation.

Published
1993
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31. Biochemical and Autoradiographical Determination of Protein Synthesis in Experimental Brain Tumors of Rats

Author

K.-A. Hossmann, R. Widmann, M. Kocher, and Ralf-Ingo Ernestus

Subjects
Male, chemistry.chemical_classification, medicine.diagnostic_test, Brain Neoplasms, Proteolysis, Brain tumor, Rats, Inbred Strains, Endogeny, Biology, medicine.disease, Biochemistry, Neoplasm Proteins, Rats, Amino acid, Cellular and Molecular Neuroscience, chemistry, Leucine, Glioma, medicine, Protein biosynthesis, Animals, Autoradiography, Specific activity
Abstract

The rate of leucine incorporation into brain proteins was studied in rats with experimental brain tumors produced by intracerebral transplantation of the glioma clone F98. Incorporation was measured with [14C]leucine using a controlled infusion technique for maintaining constant specific activity of [14C]leucine in plasma, followed by quantitative autoradiography and biochemical tissue analysis. After 45 min the specific activity of free [14C]leucine in plasma was 2.5-3 times higher than in brain and brain tumor, indicating that the precursor pool for protein synthesis was fueled both by exogenous (plasma-derived) and endogenous (proteolysis-derived) amino acids. Endogenous recycling of amino acids amounted to 73% of total free leucine pool in brain tumors and to 60-70% in normal brain. Taking endogenous amino acid recycling into account, leucine incorporation was 78.7 +/- 16.0 nmol/g of tissue/min in brain tumor, and 17.2 +/- 4.2 and 9.7 +/- 3.3 nmol/g/min in normal frontal cortex and striatum, respectively. Leucine incorporation within tumor tissue was markedly heterogeneous, depending on the local pattern of tumor proliferation and necrosis. Our results demonstrate that quantitative measurement of leucine incorporation into brain proteins requires estimation of recycling of amino acids derived from proteolysis and, in consequence, biochemical determination of the free amino acid precursor pool in tissue samples. With the present approach such measurements are possible and provide the quantitative basis for the evaluation of therapeutic interventions.

Published
1992
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32. Effect of alpha-chloralose, halothane, pentobarbital and nitrous oxide anesthesia on metabolic coupling in somatosensory cortex of rat

Author

G. Mies, K.-A. Hossmann, and M. Ueki

Subjects
Male, Pentobarbital, Nitrous Oxide, Stimulation, Somatosensory system, chemistry.chemical_compound, Animals, Medicine, business.industry, Chloralose, Rats, Inbred Strains, Somatosensory Cortex, General Medicine, Rats, Glucose, Anesthesiology and Pain Medicine, medicine.anatomical_structure, chemistry, Cerebral cortex, Anesthesia, Anesthetic, Anesthesia, Intravenous, Halothane, Forelimb, Anesthesia, Inhalation, business, medicine.drug
Abstract

The effect of various anesthetics on the functional-metabolic coupling of cerebral cortex was studied in rats submitted to unilateral somatosensory stimulation. The regional cerebral metabolic rate of glucose (CMRglc) was measured autoradiographically using the 2-deoxyglucose method, and somatosensory activation was carried out by electrical stimulation of the left forepaw. In animals treated with 70% nitrous oxide, 0.5% halothane/70% nitrous oxide or 40 mg/kg pentobarbital, CMRglc of somatosensory cortex did not change despite generation of primary evoked cortical potentials. Anesthesia with 80 mg/kg alpha-chloralose, in contrast, led to a focal increase of CMRglc in the primary somatosensory cortex from 52.1 +/- 18.3 to 73.1 +/- 18.9 mumol/100 g/min (means +/- s.d.). Metabolic activation was strictly confined to the forelimb (FL) area of somatosensory cortex, and it exhibited a laminar pattern with maximal activation in layers I, II and IV. The preservation of functional-metabolic coupling under a surgical dose of chloralose renders this anesthetic particularly suited for the investigation of coupling processes under conditions where the experimental requirements preclude the use of unanaesthetized animals.

Published
1992
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33. Ischemic Thresholds of Cerebral Protein Synthesis and Energy State following Middle Cerebral Artery Occlusion in Rat

Author

Günter Mies, Y Xie, K.-A. Hossmann, S. Ishimaru, and K. Seo

Subjects
Male, medicine.medical_specialty, Cerebral arteries, Ischemia, Brain Ischemia, Brain ischemia, chemistry.chemical_compound, Adenosine Triphosphate, Leucine, Internal medicine, medicine.artery, Occlusion, medicine, Animals, Chemistry, Brain, Blood flow, Anatomy, Cerebral Arteries, medicine.disease, Rats, Inbred F344, Rats, medicine.anatomical_structure, Endocrinology, Neurology, Cerebral cortex, Cerebrovascular Circulation, Protein Biosynthesis, Middle cerebral artery, Neurology (clinical), Energy Metabolism, Cardiology and Cardiovascular Medicine, Adenosine triphosphate
Abstract

The ischemic threshold of protein synthesis and energy state was determined 1, 6, and 12 h after middle cerebral artery (MCA) occlusion in rats. Local blood flow and amino acid incorporation were measured by double tracer autoradiography, and local ATP content by substrate-induced bioluminescence. The various images were evaluated at the striatal level in cerebral cortex by scanning with a microdensitometer with 75 μm resolution. Each 75 × 75 μm digitized image pixel was then converted into the appropriate units of either protein synthesis, ATP content, or blood flow. The ischemic threshold was defined as the flow rate at which 50% of pixels exhibited complete metabolic suppression. One hour after MCA occlusion, the threshold of protein synthesis was 55.3 ± 12.0 ml 100 g−1 min−1 and that of energy failure was 18.5 ± 9.8 ml 100 g−1 min−1. After 6 and 12 h of MCA occlusion, the threshold of protein synthesis did not change (52.0 ± 9.6 and 56.0 ± 6.5 ml 100 g−1 min−1, respectively) but the threshold of energy failure increased significantly at 12 h following MCA occlusion to 31.9 ± 9.7 ml 100 g−1 min−1 ( p < 0.05 compared to 1 h ATP threshold value; all values are mean ± SD). In focal cerebral ischemia, therefore, the threshold of energy failure gradually approached that of protein synthesis. Our results suggest that with increasing duration of ischemia, survival of brain tissue is determined by the high threshold of persisting inhibition of protein synthesis and not by the much lower one of acute energy failure. If the ischemic penumbra is considered to comprise the region in which cerebral protein synthesis is suppressed and energy state is preserved, it follows that the size of the penumbra decreases with the duration of ischemia.

Published
1991
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34. Keine Störung der elektrischen Aktivität des Gehirns der Katze in einem 4,7 T starken statischen Magnetfeld

Author

K.-A. Hossmann, O. Kloiber, and Y. Okada

Subjects
Physics, medicine.diagnostic_test, Champ magnetique, Electroencephalography, Intensity (physics), Electrophysiology, Nuclear magnetic resonance, Amplitude, nervous system, Somatosensory evoked potential, Physiology (medical), Time course, medicine, Neurology (clinical), Eeg frequency analysis, Neuroscience
Abstract

The effect of increasing static magnetic field strength up to 4.7 Tesla on the electrical function of the cat brain was studied by EEG frequency analysis and recording of somatosensory evoked potentials. While the latencies of the peaks P6 and P10 of the somatosensory evoked potentials were stable during the time course of the experiment, EEG intensity, EEG frequency index and the P10/N15 amplitude showed substantial fluctuations

Published
1990
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35. Determination of endogenous serum proteins in normal and oedematous brain tissue of cat by rocket and crossed immunoelectrophoresis

Author

J. Szymas and K.-A. Hossmann

Subjects
Pathology, medicine.medical_specialty, Brain Edema, Blood volume, Immunoelectrophoresis, Cerebral edema, Antigen, Animals, Medicine, Dominance, Cerebral, Serum Albumin, Antiserum, medicine.diagnostic_test, Brain Neoplasms, business.industry, Albumin, Blood Proteins, Glioma, Blood Protein Electrophoresis, medicine.disease, Blood proteins, Extravasation, Immunoglobulin G, Cats, Surgery, Neurology (clinical), business, Neoplasm Transplantation
Abstract

A quantitative method for determination of endogenous serum proteins has been established and tested in an experimental model of peritumoural brain oedema in cats. Rocket and crossed immunoelectrophoresis were applied for determination of total serum proteins, albumin, IgG and haemoglobin in blood and brain homogenates. Modifications such as the use of non-ionic detergents and of antisera with different specificity were established for each antigen under investigation. The content of total serum proteins, albumin and IgG was substantially higher in tumour and peritumoural brain tissue than in the non-oedematous brain. The measurement of haemoglobin allowed the calculation of blood volume and, in consequence, the differentiation between intra- and extravascular serum proteins. The results are in line with earlier measurements obtained by different analytical methods and demonstrate that the present technique provides a reliable approach for the quantitative assessment of serum protein extravasation.

Published
1990
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36. Cerebral Blood Flow, Glucose Utilization, Regional Glucose, and ATP Content during the Maturation Period of Delayed Ischemic Injury in Gerbil Brain

Author

K.-A. Hossmann, Günter Mies, and Wulf Paschen

Subjects
Male, medicine.medical_specialty, Time Factors, Cell Survival, Ischemia, Hemodynamics, Gerbil, Brain Ischemia, Adenosine Triphosphate, Internal medicine, medicine, Animals, Neurons, Chemistry, Deoxyglucose, Brain, Blood flow, medicine.disease, Glucose, Endocrinology, Neurology, Cerebral blood flow, Cerebrovascular Circulation, Neurology (clinical), Halothane, Gerbillinae, Cardiology and Cardiovascular Medicine, Perfusion, medicine.drug
Abstract

Coupling between local perfusion and metabolism was examined in Mongolian gerbils during the development of delayed neuronal death using a combination of double-tracer autoradiography and imaging of local energy state. Animals were anesthetized with 1.5% halothane and forebrain ischemia was produced by occluding both common carotid arteries. After 5 min of ischemia, brains were recirculated for 6 h and 1, 2, or 4 days. At the end of the experiment, regional cerebral blood flow (CBF) and glucose utilization (CMRglc) were determined in identical brain sections with [131I]iodoantipyrine and [14C]deoxyglucose, respectively. Adjacent sections were taken for imaging of ATP and glucose using substratespecific bioluminescence reactions. In the CA1 subfield of control animals, CBF and CMRglc amounted to 81 ± 8 ml 100g−1 min−1 and 69 ± 2 μmol 100 g−1 min-1, respectively, and the calculated CBF/CMRglc ratio was 1.18 ± 0.12 ml/μmol (mean ± SD). After ischemia, the CBF/CMRglc ratio increased to 1.31 ± 0.14, 1.43 ± 0.16, 1.45 ± 0.16, and 1.56 ± 0.18 ml/μmol following 6 h and 1, 2, or 4 days recirculation, respectively. Glucose levels did not change during the 6 h to 4 day recirculation period in the hippocampal CA1 subfield. In the same region, ATP levels were unchanged during 6 h to 2 day postischemic recovery but reduced to about 70% after 4 days of recirculation. The results indicate that a mismatch of the flow-metabolism couple following transient ischemia does not appear to contribute to the postischemic maturation of delayed neuronal death in selectively vulnerable brain regions.

Published
1990
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37. Proton relaxation enhancement in experimental brain tumors—In vivo NMR study of manganese(III)TPPS in rat brain gliomas

Author

K.-A. Hossmann, M. Kocher, M. Höhn-Berlage, and Kurt Bockhorst

Subjects
Male, Porphyrins, medicine.medical_treatment, Tetraphenylporphine sulfonate, Intraperitoneal injection, Biomedical Engineering, Biophysics, Contrast Media, Grey matter, chemistry.chemical_compound, Nuclear magnetic resonance, In vivo, Glioma, Mole, medicine, Animals, Radiology, Nuclear Medicine and imaging, Manganese, Brain Neoplasms, business.industry, Relaxation (NMR), Histology, medicine.disease, Magnetic Resonance Imaging, Rats, medicine.anatomical_structure, chemistry, Nuclear medicine, business
Abstract

The effect of manganese(III)tetraphenylporphine sulfonate (MnTPPS) on the relaxation enhancement of NMR images (MRI) was studied in experimental brain tumors in rats. Brains were inoculated with the glioma cell line F98 12 to 19 days before the NMR experiment, and the effect of MnTPPS (0.25 mmol/kg body weight) was investigated 2 and 4 days after intraperitoneal injection. After MnTPPS addition tumors could be clearly distinguished by the brightness from the surrounding brain whereas they were barely visible without contrast enhancement. At SE time of 25 msec and TR time of 3500 msec the ratio of magnetization values of tumor versus normal grey matter increased from 0.98 ± 0.08 to 1.24 ± 0.09 (means ± SD). When TR was shortened to 1100 msec contrast enhancement further increased to 1.77 ± 0.25. These results demonstrate for the first time that MnTPPS is an efficient agent for contrast enhancement of brain tumors.

Published
1990
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38. Pattern of neuronal vulnerability in the cat hippocampus after one hour of global cerebral ischemia

Author

B. Grosse Ophoff, R. Schmidt-Kastner, and K.-A. Hossmann

Subjects
Pathology, medicine.medical_specialty, Glial fibrillary acidic protein, Dentate gyrus, Fissipedia, Ischemia, Anatomy, Granular layer, Biology, medicine.disease, biology.organism_classification, Hippocampus, Pathology and Forensic Medicine, Cellular and Molecular Neuroscience, medicine.anatomical_structure, nervous system, Ischemic Attack, Transient, Intensive care, Cats, medicine, Carnivora, biology.protein, Animals, Neurology (clinical), Neuron
Abstract

The dorsal hippocampus of cat was investigated by light microscopy and immunohistochemistry following 1 h global cerebral ischemia and various recirculation times from 1 day to 1 year. Complete ischemia was produced by combining hypotension with intrathoracic occlusion of major arteries. Post-ischemic resuscitation was carried out using an intensive care regimen with continuous neurophysiological monitoring. Brains of controls (n = 4) and post-ischemic animals (n = 12) were fixed in formaldehyde and prepared for histology and immunohistochemistry of glial fibrillary acidic protein (GFAP). In all post-ischemic animals the hilus and the regio superior of dorsal hippocampus which encompasses the CA1 subfield were severely damaged. Neurons in these regions exhibited the typical sequela of neuronal death. GFAP staining revealed vivid astroglial proliferation in stratum lacunosum-moleculare and stratum oriens. Changes in the regio inferior of dorsal hippocampus, i.e., CA3 subfield, and in dentate gyrus granular layer, were variable. Although most animals exhibited moderate to severe neuronal and glial alterations, groups of surviving cells were observed in the stratum oriens and in the granular layer of dentate gyrus. In one animal the majority of CA3 pyramidal cells and granule cells was preserved. These findings demonstrate that after 1 h of complete cerebral ischemia dorsal hippocampus exhibits two different types of injury: a consistent pattern of selective vulnerability in the hilus and the regio superior, and a variable pattern of non-selective injury in the regio inferior and dentate gyrus. The two patterns can be best explained by intrinsic (pathoclitic) and extrinsic (hemodynamic/edema) factors, respectively and are likely to represent basically different mechanisms of ischemic injury.

Published
1990
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39. Abstract of the 68th Meeting (Spring Meeting) 6–9 March 1990, Heidelberg

Author

B. Sakmann, J. Schrader, B. Brenner, H. Murer, J. Boeckh, H. O. Handwerker, P. HonerjÄger, M. Dugas, G. Wang, A. DeLuca, H. Brinkmeier, B. Fakler, T. Pröbstle, R. Rüdel, J. -A. Pohl, H. Meves, B. Kroll, S. Bremer, B. Tümmler, E. Frömter, J. S. Schwegler, W. Steigner, S. Silbernagl, Michael Pusch, P. Niemann, J. Schmidtmayer, W. Ulbricht, G. Hansen, U. Lönnendonker, B. Neumcke, R. Eickhorn, D. Hornung, H. Antoni, R. Penner, E. Neher, H. Takeshima, S. Nishimura, S. Numa, W. Melzer, D. Feldmeyer, B. Pohl, P. Zöllner, T. H. Müller, D. Swandulla, U Misgeld, V. Ya. Ganitkevich, G. Isenberg, A. Cavalié, T. J. A. Allen, W. Trautwein, Siegried Pelzer, Yaroslav M. Shuba, Tatsuya Asai, Wolfgang Trautwein, Arthur M. Brown, Lutz Birnbauner, Terence F. McDonald, Dieter Pelzer, R. Eckert, J. Hescheler, W. Rosenthal, S. Offermann, D. Krautwurst, G. Schultz, Helmut Kettenmahn, J. Trotter, Alexe J N. Verkhratsky, Alexej N. Savtchenko, Alexej N. Verkhratsky, A. Schiefer, U. Klöckner, L. D. Partridge, S. SchÄfer, P. Jonas, D. S. Koh, K. Kampe, M. Hermsteiner, W. Vogel, C. K. Bauer, J. R. Schwarz, R. H. A. Fink, E. Wettwer, R. Weik, E. Schlatter, M. Bleich, M. Granitzer, T. Leal, W. Nagel, J. Crabbé, F. Lang, E. Kahn, F. Friedrich, M. Paulmichl, M. Hammerer, K. Maly, H. Grunicke, T. Böhm, B. Nilius, H. Gögelein, D. Dahlem, H. Weiss, S. Waldegger, E. Woell, R. Paulmichl, J. P. Ruppersberg, K. H. Schröter, M. Stocker, O. Pongs, R. Wittka, G. Boheim, R Lichtinghagen, C. K. Augustine, W. Stühmer, Dorothe Hoppe, D. Hoppe, K. E. Zittlau, C. Walther, H. Hatt, C. Franke, S. Quasthoff, E. Wischmeyer, H. Jockusch, M. Friedrich, K. Benndorf, G. Bollmann, Hj. Hirche, F. Hollunder-Reese, M. Mohrmann, R. Greger, S. Weber-Schürholz, T. Schürholz, M. Akabas, D. Landry, Q. Al-Awqati, A. H. Guse, G. Gercken, W. Meyerhof, H. -J. Westphale, U. Kerstins, H. Oberleithner, M. Tilmann, K. Kunzelmann, T. Klitsch, D. Siemen, A. Draguhn, T. A. Verdoorn, D. B. Pritchett, P. H. Seeburg, P. Malherbe, H. Möhler, J. Dudel, P. Stern, F. Zufall, J. Rosenheimer, D. O. Smith, R. Dörner, K. Ballanyi, W. -R. Schlue, B. Kalthof, L. Pott, C. Busch, T. Konno, M. Stenql, Ch. Reinhardt, H. Kaiser, R. Baumann, M. Wilimzig, R. Eichenlaub, E. Neumann, V. Lessmann, K. Gottmann, I. D. Dietzel, B. U. Keller, Y. Yaari, A. Konnerth, K. H. Backus, T. Giller, F. Knoflach, P. Pflimlin, G. Trübe, G. von Blankenfeld, S. Ymer, H. Sontheimer, M. Ewert, H. Kettenmann, R. Schneggenburger, D. Paschke, D. F. Hülser, J. Ubl, H. A. Kolb, J. Ströttchen, S. Boheim, F. Wehner, D. Guth, R. K. H. Kinne, H. R. Polder, D. Bödeker, Susanne Hoppe, H. Höller, W. Hampe, H. Ruf, I. Schulz, M. Dehlinger-Kremer, T. Ozawa, L. Vasilets, G. Schmalzing, K. MÄdefessel, H. Biel, W. Schwarz, B. C. Burckhardt, N. Stallmach, H. MairbÄurl, J. F. Hoffman, E. Schömig, A. Heuner, B. O. Göbel, W. Siffert, A. Butke, G. Hoffmann, M. -K. Meyer zu Brickwedde, H. Vetter, R. Düsing, D. Rosskopf, U. Osswald, J. Steffgen, H. Koepsell, H. Martens, M. Rübbelke, G. GÄbel, J. Arens, J. Stabel, Y. Fischer, J. Thomas, H. Rose, H. Kammermeier, Thomas Munsch, Joachim W. Deitmer, B. Engelmann, J. Duhm, D. Gunzel, S. Galler, H. Fischer, W. Clauss, W. Van Driessche, A Köckerling, JD Schulzke, D Sorgenfrei, M Fromm, B. Simon, V. Ganapathy, F. H. Leibach, G. Burckhardt, R. Krattenmacher, Rosita Voigt, S. Dietrich, A. Leyssens, S. L. Zhang, R. Weltens, P. Steels, B. Hoffmann, M. Heinz, B. Habura, A. Dörge, G. Rechkemmer, W. von Engelhardt, O. StrauB, M. Wiederholt, D. -G. Margineanu, K. M. Kreusel, M. Fromm, U. Lempart, D. Sorgenfrei, U. Hegel, A. J. Augustin, R. . Goldstein, E. Purucker, J. Lutz, B. Illek, K -P. Thiele, JS. Schwealer, J. Dittmer, C. Bauer, K. -U. Eckardt, R. Neumann, A. Kurtz, H. Fromm, J. D. Schulzke, P. Clausen, A. Krohn, S. Lüderitz, K. Hierholzer, U. Kersting, L. Woinowski, R. Gro\mann, X. U. Bin, F. Ellendorff, R. Nitschke, U. Fröbe, H. Scholz, R. della Bruna, H. Ehmke, P. B. Persson, M. Seyfarth, H. R. Kirchheim, M. S. Dietrich, N. Parekh, M. Steinhausen, C. P. Bührle, R. Nobiling, K. J. Ullrich, G. Rumrich, S. Klöss, F. Papavassiliou, J. Hoyer, C. Schmitt, A. Jungwirth, M. Ritter, H. J. Westphale, C. Bevan, C. Theiss, Liliana Denek, Johann S. Schwegler, Roland SchÄfer, Albert J. Augustin, August Heidland, B. Nafz, A. Just, M. Steidl, G. Pinggera, R. Gerstberger, H. Schütz, E. Simon, E. Lohrmann, B. Masereel, J. Delarge, H. J. Lang, H. C. Englert, D. Caliebe, M. Mályusz, P. Wrigge, G. Gronow, N. Klause, H. Zinnert, H. Fagel, W. Jelkmann, Ch. Weiss, R. Keil, W. Schmidt, C. Kröger, E. G. Brabant, A. Hilgendorf, S. Strauch, F. Lane, A. Prick, N. Golenhofen, S. Mildenberger, B. Flemming, D. Roloff, T. Wronski, G. Drews, A. Debuyser, J. C. Henquin, M. B. Jackson, S. A. DeRiemer, A. Schmid, S. Schnefel, A. Pröfrock, K. -D. Hinsch, J. Milz, G. Lamprecht, U. Seidler, W. Silen, O. Aziz, W. Reschke, G. Fischer, N. De Decker, T. Hayes, G. Coast, E. Van Kerkhove, F. von zur Mühlen, F. Eckstein, U Hegel, CJ Bentzel, EO Riecken, C. Siemer, P. Rothenpieler, E. Smith, K. R. Lutnicki, J. T. Wróbel, A. Ledwożyw, E. PietraŚ, S. Sender, Klaus D. Jürgens, T. Kleinschmidt, F. Werkmeister, H. Kiwull-Schöne, P. Kiwull, J. Vahle, M. Ott, R. E. Zimmermann, J. G. Elsing, D. Million, P. Zillner, M. Thiel, H. Bardenheuer, K. Peter, J. Fandrey, C. P. Siegers, H. Rupp, V. Elimban, N. S. Dhalla, I. Morano, B. Agostini, M. Mühleisen, W. F. H. M. Mommaerts, K. Ono, M. Wussling, W. Schenk, W. Boldt, P. Lipp, K. Schüttler, G. Szymanski, M. F. Wendt-Gallitelli, J. W. Herzig, H. Depersin, G. Grupp, I. Grupp, H. G. Glitsch, H. Pusch, Ch. Zylka, M. Brāndle, R. Jacob, T. Stein, W. Isselhard, J. Sturz, T. Minor, P. Wingenfeld, B. Siegmund, T. Klietz, P. Schwartz, H. M. Piper, Christa Linder, Stefan SchÄfer, Gerd Heusch, B. F. Becker, N. Reinholz, P. Raschke, B. Leipert, E. Gerlach, B. Dierberger, R. W. Gülch, M. Leverkus, T. Mitsuiye, U. Pohl, S. Y. Wang, R. Meyer, H. G. Haas, H. Ph Christmann, Th Dörner, D. Hock, R. Hertel, M. Gagelmann, W. G. Forssmann, W. J. Leijendekker, G. Kissling, H. Michel, A. Goetz, M. Freya, G. Fleckenstein-Grün, Jochen D. Schipke, Yasuhiko Harasawa, Seiryo Sugiura, Joe Alexander, Daniel Burkhoff, L. Kling, B. Müller-Beckmann, M. Schroth, G. Sponer, E. Böhm, K. Strein, A. Dorszewski, G. Arnold, G. K. Pike, D. J. Bryant, M. L. Roberts, R. H. Fink, Ch. Ross, A. Skyschally, R. Schulz, C. Linder, G. Heusch, J. D. Schipke, D. Burkhoff, J. Alexander, F. Gollnick, Kh. Peter, R. Franken-Weyers, M. M. Borst, A. Deussen, S. Pöpping, H. Hose, K. H. Strotmann, B. Lukascek, T. Karnath, K. Güttier, W. Klaus, K. Haverkampf, M. Guhlmann, S. Schmidt-Ott, U. Heuschen, G. Mall, G. Pfitzer, J. Rösch, A. Arner, J. C. Rüegg, K. Kröger, V. ThÄmer, Thomas Ehring, Volker ThÄmer, B. D. Guth, Ph A. Schnabel, A. Schmiedl, M. M. Gebhard, J. Richter, H. J. Bretschneider, R. J. Oudiz, Ph. Schnabel, J . Richter, H. Watanabe, R. Spahr, O. Obst, H. Mertens, A. Mülsch, R. Busse, D. Lamontagne, K. Herlan, A. Huang, E. Bassenae, J. R. L. Mackert, L. Schilling, A. A. Parsons, M. Wahl, M. Ph. Christmann, F. Thimm, M. Frey, a. A. Fleckenstein, H. Theilen, U. Göbel, W. Kuschinsky, Th. Elbert, M. Tafil-Klawe, H. Rau, W. Lutzenberger, A. Fleckenstein, H. Forst, M. Haller, C. Santjohanser, L. Lauterjung, Y. Smieško, D. J. Lang, P. C. Johnson, H. Schröck, T. Elbert, B Geiger, G. Koch, H. E. Koralewski, F. H. Perschel, K. Wagner, U. Krüger, M. Albrecht, G. Hohlbach, N. Maassen, M. Foerster, J. Mühling, F. Bari, K. Pleschka, H. D. Schmidt, H. Gro, W. Loock, C. Stick, U. Diefenbacher, D. Gronewold, M. Tobinsky, A. Walther-Behrends, E. Witzleb, M. Brummermann, R. E. Reinertsen, H. Rogausch, W. M. Rohn, H. Acker, M. Delpiano, E. Dufau, J. Hentschel, H. Heller, K. -D. Schuster, R. Siekmeier, H. Kronenberger, H. Lintl, Ch. F. Schiller-Scotland, J. Gebhart, J. Heyder, J. Meier-Sydow, W. Stahlhofen, K. Mottaghy, C. Geisen, W. Richter, J. Beckman, W. Marek, W. T. Ulmer, A. E. Thiele, F. Raschke, J. H. Peter, G. Hildebrandt, T. Kullmer, G. Kozianka-Burghof, M. E. Schlaefke, H. Gnuschke, T. Schaefer, D. Schaefer, C. Schaefer, Ronald J. Bradley, Raimund Sterz, Klaus Peper, R. Benterbusch, Th. Kraft, L. C. Yu, H. J. Kuhn, K. Blankenbach, G. Asmussen, I. Kunze, K. -S. Pieper, J. Steinmetz, H. Schmidt, P. Krippeit-Drews, U. Hübschen, A. C. Nacimiento, D. Günzel, W. Rathmayer, U. Gaunitz, D. Költgen, E. Zachar, B. Soltau, L. De Martino, W. Hasselbach, F. Kössler, P. Lange, G. Küchler, C. Zeugner, J. Van Eyk, R. S. Hodges, H. Lorkovic, N. Clemens, P. Scheid, Th. Noack, P. Deitmer, K. Golenhofen, E. Lammel, Andrea Welling, Jochen Felbel, Franz Hofmann, S. Katoch, T. Watanabe, K. Mandrek, K. Milenov, K. Hammer, W. Rössler, H. Sann, Fr -K. Pierau, H. Nguyen-Duong, P. Schneider, F. Stahl, A. Lepple-Wienhues, C. Korbmacher, H. Haller, M. Gebauer, U. Willner, C. Bialojan, M. Lengsfeld, V. Kyrtatas, Peter C. Dartsch, P. J. Boels, W. Fischer, T. Lenz, U. Thei, V. A. W. Kreye, T. Ohkubo, H. Kupp, M. Vonderlage, V. Schreiner, M. Dorlöchter, M. Brinkers, A. Irintchev, A. Wernig, B. Langenfeld, W. Finger, H. Wolburg, A. Beer, Ch. Schwejda, D. Scheller, U. Heister, F. Tegtmeier, Thomas Knöpfel, Andreas Spuler, Peter Grafe, Beat GÄhwiler, M. Bijak, U. Misgeld, W. Müller, G. Rausche, F M. Leweke, D. Bingmann, I. Moraidis, E. -J. Speckmann, M. Madeja, U. Mu\hoff, A Lehmenkühler, D. Kuhlmann, M. Hans, H. D. Lux, H. StrÄub, J. Waiden, R. E. Baker, R. Grantyn, M. Perouansky, K Kraszewski, Chr Lehmenkühler, H. U. Dodt, W. ZieglgÄnsberger, H. Pawelzik, W. ZieglgÄngsberger, K. Mann, H. Wiethölter, D. Albrecht, J. Dreier, E. Ficker, H. Beck, B J. Corrette, F. Dreyer, H. Repp, J. Dreessen, G. J. Augustine, A. Lehmenkühler, D. Büsselberg, B. Heimrich, H. L. Haas, S. Birnstiel, B. Schönrock, U. Altrup, H. Reith, C. Alzheimer, G. ten Bruagencate, B. Fruhstorfer, E. Mignot, S. Nishino, W. C. Dement, C. Guilleminault, Christa Simon-Oppermann, Olaf Günther, J. Stehle, S. Reuss, A. Seidel, R. Riemann, L. Vollrath, Susanne Reimer, Volker HölIt, U. Sonnhof, J. Krupp, H Claus, P. Hinckel, H. B. H. Dick, C. Hiemke, A. Jussofie, T. Dorn, S. Uhlig, O. W. Witte, B. Bother, M. Eiselt, H. Witte, ö Zwiener, M Rother, H. Eiseit, A. Taghavy, A. KrÄtzer, H. Clusmann, U. Heinemann, F. Block, K. -H. Sonatg, M. Falkeristein, J. Hohnsbein, J. Hoormann, A. Frieling, I. M. Tarkka, W. Kullmann, B. Bromm, M. Chr Hirsch, H. Wissing, H. A. Braun, P. Igelmund, F. W. Klu\mann, W. H. Ehrenstein, N. Yakimoff, S. Mateeff, M. L. Zeise, J. Arriagada, A. Teschemacher, T. Pöppelmann, R. Köhling, P. Boerrigter, K. Anders, W. Ohndorf, R. Dermietzel, D. W. Richter, T. R. Tölle, J. M. Castro-Lopes, Klinische Neuropharmakologie, J. Sandkühler, J. D. Leah, T. Herdegen, M. Zimmermann, D. Vaitl, H. Gnippe, M. K. Herbert, M. K. C. Mengel, K. -D. Kniffki, R. Linke, C. Vahle-Hinz, J. Schenda, K. Matsumura, Q. -G. fu, C. Forster, W. D. Hutchison, C. R. Morton, J. Aschoff, Z. Wilhelm, S. W. Schwarzacher, M Wasserschaff, M. Hörner, H. Kümmel, U. Windhorst, J. L. Feldman, K. Schmid, A. S. Foutz, M. Denavit-Saubié, M. A. Pak, P. Wehling, C. Evans, G. Bandara, F. Awiszus, H. Feistner, H. -J. Heinze, M. Illert, M. Wasserschaff, D. Kleinebeckel, G. Böhmer, W. Schauer, H. -H. Abel, D. Klü\endorf, H. P. Koepchen, W Jarolimek, St König, J. Czachurski, H. Seller, R. L. Meckler, E. M. McLachlan, A. Boczek-Funcke, H. -J. HÄbler, W. JÄnig, M. Michaelis, K. Dembowsky, S. Königr, Harald Rau, M. Unger, G. Merker, J. Roth, E. Zeisberger, H. Gao, M. Hunold, F. Kirchner, K. Takano, K. Schulze, M. Pokorski, Y. Sakakibara, A. Masuda, T. Morikawa, B. Ahn, S. Takaishi, P. -E. Paulev, Y. Honda, G. Flügge, E. Fuchs, S. König, U. Th. Eysel, R. Schmidt-Kastner, W. Skrandies, T. Geib, C. Baumann, K. -F. Schmidt, A. G. Knapp, J. E. Dowling, M. Kuba, N. Toyonaga, Z. Kubová, P. Jacobi, G. N. Nöll, Ch. Baumann, M. Tabata, Ch. Martin, H. Meissl, Th. Knottenberg, H. Scheibner, Hans P. Zenner, Ulrike Zimmennann, Alfred H. Gitter, D. Ding, J. W. T. Smolders, R. Klinke, I. Boekhoff, K. Raming, J. Krieger, E. Tareilus, J. Strotinann, H. Breer, D. Schild, J. A. DeSimone, S. Hellwig, A. H. Gitter, P. K. Plinkert, H. P. Zenner, M. Koltzenbwg, E. Pinter, K. SchÄfer, R. Necker, U. Hanesch, B. Heppelmann, R. F. Schmidt, S. Mense, U. Hoheisel, K. H. Steen, F. Anton, P. W. Reek, G. R. Lewin, S. B. McMahon, G. Heyer, O. P. Hornstein, W. Klement, J. O. Arndt, W. Maeerl, G. GrÄmer, K. Schepelmann, K. Me\linger, H. -G. Schaible, R. D. Treede, R. A. Meyer, J. N. Campbell, D. Claus, B. Neundörfer, R. Ernst, A. M. Tick-Waider, F. Bretschneider, R. C. Peters, P. F. M. Tennis, P. F. M. Teunis, D. Hoheisel, R. Scherotzke, A. Bub, G. Manzl, C. Jessen, B. Nuesslein, I. Schmidt, J. Wetzig, M. Reiser, N. Bregenzer, R. J. von Baumgarten, E. Mohr, H. Krzywanek, G. Warncke, K. -L. Schuchmann, H. Linow, F. H. Klu\mann, U. Redlin, G. Heldmaier, A Bamler, A. Koller, S. Felber, C. Haid, K. Wicke, E. Raas, Wang Xuemin, Chen Kerning, Shi Ying, Shi Hanping, Günther Warncke, R. Voisord, P. C. Dortsch, E. Betz, U. Karbach, S. Walenta, M. W. Gross, W. Mueller-Klieser, P. Vaupel, P. Okunieff, W. -K. Mayer, M. Stohrer, W. Krüger, W. Müller-Klieser, M. Strupp, P. Weial, H. Bostock, K. Piwernetz, R. Renner, P. Grafe, J. Lankers, W. Zangemeister, K. Kunze, S. Tries, H. Heinle, N. V. Beckerath, W. Maier-Rudolph, G. Mehrke, K. Günther, L. Goedel-Meinen, J. Daut, A. Kopp, T. Noll, A. Goellner, S. Gerlach, H. F. Teutsch, K. Schienger, R. Schwab, M. Höckel, Z. Fotev, M. Nienhaus, Gabriele Kaczmarczyk, Dinah Richter, Gabriele Korte, J. Förther, H. W. Reinhardt, R. Schreiber, J. Rupp, G. Murphy, J. Fingerle, O. Kloiber, T. Miyazawa, M. Höhn-Berlage, K. -A. Hossmann, H. Schad, W. Heimisch, R. Blasini, F. Haas, M. Mendier, A. Spuler, F. Lehmann-Hom, U. Wolfram, M. Fenske, N. Sachser, Ch. Weis, W. Marktl, B. Kopta, N. Klammer, B. Rudas, H. Pohl, A. Nienartowicz, W. Moll, M. Klempt, S. Blum, H. Bühler, I. Lichtenstein, A. Novak, H. Siebe, and K. Peper

Subjects
0303 health sciences, Physiology, Chemistry, Clinical Biochemistry, Tibialis Anterior, Human physiology, 030204 cardiovascular system & hematology, Pharmacology, Spring (mathematics), Article, Atrial Natriuretic Peptide, 03 medical and health sciences, 0302 clinical medicine, Atrial natriuretic peptide, Physiology (medical), Spreading Depression, Capsaicin, Extensor Digitorum Longus, 030304 developmental biology
Published
1990

40. Immunohistochemical study of glial reaction and serum-protein extravasation in relation to neuronal damage in rat hippocampus after ischemia

Author

R. Schmidt-Kastner, K.-A. Hossmann, and J. Szymas

Subjects
Male, Pathology, medicine.medical_specialty, Ischemia, Hippocampal formation, Hippocampus, Brain Ischemia, Capillary Permeability, Brain ischemia, Glial Fibrillary Acidic Protein, medicine, Animals, Vimentin, Neurons, Staining and Labeling, Glial fibrillary acidic protein, biology, General Neuroscience, Dentate gyrus, S100 Proteins, Rats, Inbred Strains, Blood Proteins, Granule cell, medicine.disease, Immunohistochemistry, Extravasation, Rats, medicine.anatomical_structure, nervous system, biology.protein, Neuroglia
Abstract

Transient forebrain ischemia of 30 min duration was produced in anaesthetized rats by four-vessel occlusion. After survival periods of 3 h to three days brains were perfusion-fixed and sections through the mid-dorsal hippocampus were processed for conventional staining and immunohistochemical analysis. Neuronal damage in the hilus was manifested 3-8 h after ischemia; neurons in the CA1 and CA2 sector suffered delayed neuronal death after 48-72 h whereas the dentate gyrus and the CA3 sector were normal. Vasogenic edema formation was visualized using antibodies against rat serum-proteins, serum albumin and immunoglobulins. By 3 h after ischemia, only faint and diffuse serum-staining was detected. At 8 h survival, weak astrocytic-staining was present. After 24-72 h CA1-CA2 exhibited massive serum extravasation. The molecular layer of the dentate gyrus showed edema formation in the absence of granule cell damage. The glial reaction was studied using antibodies against glial fibrillary acidic protein, vimentin and S-100 protein. Glial fibrillary acidic protein and S-100 protein-staining increased in areas with either edema or neuronal damage. In contrast, changes in vimentin were only detected in areas with neuronal necrosis. The observations demonstrate that following 30 min of ischemia neuronal damage is accompanied by changes in blood-brain barrier function and reactive glial alterations. The dissociation between neuronal necrosis and astroglial hypertrophy and hyperplasia reflects differences in cellular responsiveness which constitute inherent features of postischemic hippocampal injury.

Published
1990
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42. [Therapeutically induced arteriogenesis in the brain. A new approach for the prevention of cerebral ischemia with vascular stenosis]

Author

H-J, Busch, I, Buschmann, E, Schneeloch, C, Bode, G, Mies, and K-A, Hossmann

Subjects
Disease Models, Animal, Treatment Outcome, Animals, Brain, Granulocyte-Macrophage Colony-Stimulating Factor, Neovascularization, Physiologic, Carotid Stenosis, Angiogenic Proteins, Brain Ischemia, Rats
Abstract

Stroke is the leading cause of disability and a major cause of death in Germany and the western world. Ischemic stroke involves different pathophysiologic mechanisms such as thromboembolic vascular occlusion, cerebral micro- or macroangiopathy, extracranial arterial stenosis, and cardiac embolism. Experimental and clinical studies have shown that arteriogenesis, the adaptive growth of pre-existing collateral arteries, can be therapeutically enhanced in peripheral circulation and the heart. We examined the consequences to time course and hemodynamics of brain arteriogenesis in a chronic hypoperfusion model following systemic administration of the hemopoietic growth factor called granulocyte macrophage colony stimulating factor (GM-CSF). Treatment with GM-CSF led to the growth of intracranial collateral arteries, which improved the cerebral hemodynamic reserve and significantly reduced energy failure when brains were additionally challenged by hypotension. Therapeutically induced arteriogenesis may be of considerable interest for preventing infarction in patients with uncompensated cerebrovascular disease.

Published
2005

44. Non-invasive imaging methods for the characterization of the pathophysiology of brain ischemia

Author

K A, Hossmann

Subjects
Magnetic Resonance Spectroscopy, Animals, Humans, Magnetic Resonance Imaging, Brain Ischemia, Tomography, Emission-Computed
Abstract

Non-invasive imaging methods are increasingly used to study the evolution and therapy of brain diseases under both clinical and experimental conditions. In the animal experiment, these methods can be supplemented by invasive tissue assays to allow precise characterization of the underlying pathophysiology. Based on such an approach, this review evaluates the importance of in vivo nuclear magnetic resonance (NMR) and positron emission tomography (PET) for the understanding of the pathophysiology of brain ischemia.

Published
2004

45. Transgenic Mutants for the Investigation of Molecular Stroke Mechanisms

Author

G. Mies, K. Maeda, T. Trapp, R. Hata, and K.-A. Hossmann

Subjects
Pathology, medicine.medical_specialty, business.industry, Ischemia, Hemodynamics, Bradykinin, Brain damage, Blood flow, medicine.disease, Vascular occlusion, chemistry.chemical_compound, chemistry, Renin–angiotensin system, Medicine, medicine.symptom, business, Stroke
Abstract

Brain damage induced by focal interruption of blood flow can be differentiated in two pathophysiologically different categories: a hemodynamic type of injury, resulting in primary necrotic brain damage, and a molecular type of injury which leads to delayed or secondary brain injury [15]. Primary necrotic brain injury occurs when blood flow declines - and remains - below the threshold of energy failure. In anaesthetized laboratory animals, this threshold gradually increases from about 15% of control shortly after the onset of ischemia to about 30% after several hours of vascular occlusion [29].

Published
2004
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46. Genetically modified animals in molecular stroke research

Author

K.-A. Hossmann

Subjects
medicine.medical_specialty, business.industry, Molecular type, Ischemia, Hemodynamics, Brain damage, Blood flow, medicine.disease, Vascular occlusion, Genetically modified organism, Internal medicine, Cardiology, Medicine, medicine.symptom, business, Stroke
Abstract

Brain damage induced by focal interruption of blood flow can be differentiated in two pathophysiologically different categories: a hemodynamic type of injury, resulting in primary necrotic brain damage, and a molecular type of injury which leads to delayed or secondary brain injury [15]. Primary necrotic brain injury occurs when blood flow declines — and remains — below the threshold of energy failure. In anaesthetized laboratory animals, this threshold gradually increases from about 15% of control shortly after the onset of ischemia to about 30% after several hours of vascular occlusion [35].

Published
2004
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47. [Glutamate hypothesis of stroke]

Author

K-A, Hossmann

Subjects
Brain Chemistry, Stroke, Animals, Glutamic Acid, Humans, Electroencephalography, Cerebral Infarction, Energy Metabolism, Excitatory Amino Acid Antagonists
Abstract

Neuronal injury following focal cerebral ischemia is widely attributed to the excitatory effects of glutamate. However, critical analysis of published data on glutamate toxicity in vitro and the comparison of this data with in vivo release of glutamate and the therapeutic effect of glutamate antagonists raises doubts about a neurotoxic mechanism. An alternative explanation for glutamate-mediated injury is energy failure due to peri-infarct spreading depression-like depolarizations. These depolarizations cause a sharp increase in metabolic activity and therefore produce a mismatch between blood flow and the oxygen requirements of the tissue. The generation of peri-infarct spreading depressions and the associated metabolic workload can be suppressed by glutamate antagonists. As a result, energy failure is also prevented, and the volume of ischemic infarct decreases. Interventions to improve ischemic resistance should therefore aim at improving the oxygen supply or reducing the metabolic workload, rather than interfering with the consequences of a putative excitotoxic injury cascade.

Published
2003

48. Host-dependent tumorigenesis of embryonic stem cell transplantation in experimental stroke

Author

Mathias Hoehn, Ekkehardt Küstermann, Thorsten Trapp, Jürgen Hescheler, Christian Bührle, Franciska Erdo, Eugen Kolossov, K.-A. Hossmann, James Blunk, Melanie Föcking, Bernd K. Fleischmann, and Ying Xia

Subjects
Homeobox protein NANOG, Male, Teratocarcinoma, Pathology, medicine.medical_specialty, Transplantation, Heterologous, Biology, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, Mice, 0302 clinical medicine, Cell Movement, medicine, Animals, Humans, Transplantation, Homologous, Rats, Wistar, Stem cell transplantation for articular cartilage repair, Neurons, Brain Neoplasms, Brain, Amniotic stem cells, Cell Differentiation, Infarction, Middle Cerebral Artery, Neural stem cell, Cell biology, Rats, Neuroepithelial cell, Mice, Inbred C57BL, Stroke, Disease Models, Animal, Neurology, Amniotic epithelial cells, Neurology (clinical), Stem cell, Cardiology and Cardiovascular Medicine, 030217 neurology & neurosurgery, Adult stem cell, Stem Cell Transplantation
Abstract

The therapeutical potential of transplantation of undifferentiated and predifferentiated murine embryonic stem cells for the regeneration of the injured brain was investigated in two rodent stroke models. Undifferentiated embryonic stem cells xenotransplanted into the rat brain at the hemisphere opposite to the ischemic injury migrated along the corpus callosum towards the damaged tissue and differentiated into neurons in the border zone of the lesion. In the homologous mouse brain, the same murine embryonic stem cells did not migrate, but produced highly malignant teratocarcinomas at the site of implantation, independent of whether they were predifferentiated in vitro to neural progenitor cells. The authors demonstrated a hitherto unrecognized inverse outcome after xenotransplantation and homologous transplantation of embryonic stem cells, which raises concerns about safety provisions when the therapeutical potential of human embryonic stem cells is tested in preclinical animal models.

Published
2003

49. Roundtable discussion (Brain Edema 2002)

Author

A. Marmarou, J. T. Hoff, and K.-A. Hossmann

Subjects
Medical education, Brain edema, Psychology
Abstract

Ladies and gentlemen, I am afraid that the most difficult part of the conference begins right now. We have been asked to summarize what we have heard during the last three days, to identify the most interesting topics and to make recommendations on what to do in the future. We sat together to identify a few topics which could be of interest for the general discussion, and Tony Marmarou will be happy to introduce this list to you.

Published
2003
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