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We report here the light and electron microscopic neuropathology of the 139A-H strain of scrapie passaged in Syrian golden hamsters. The general neuropathological picture consisted of the spongiform change and severe astrocytic gliosis. The topography of prion protein (PrP) was variable, the highest signal was observed in the CA2-molecular layer, CA1-pyramidal and entorhinal cortex. The electron microscopy consisted of: 1. Spongiform vacuoles - these are always membrane bound and contain secondary vacuoles (i.e. membrane-bound compartments or vesicles within vacuoles) and curled membraned fragments. 2. Tubulovesicular structures (TVS) - these are vesicular structures of approximate 27 nm in diameter within neuronal processes - i.e. axonal terminal or dendrites. TVS are smaller and of higher electron density than synaptic vesicles. The significance of TVS remains unknown. 3. Dystrophic neurites. Dendrites or axonal preterminals and terminals filled with electron-dense bodies, including small autophagic vacuoles. 4. Apoptotic cell nuclei. 5. "Whorls", concentric arrays of membranes were visible. A significance of those structures is unknown.

The proteins' ubiquitination and their further degradation by proteasomes are crucial for cell cycle regulation, transcription and DNA replication, inflammatory response, and apoptosis. Proteasome inhibitors have recently become considered as a promising method in cancer and inflammatory disease therapy. In this study, utilizing the rat model, we try to establish the influence of proteasome inhibitor MG-132: (1) on the basis of spontaneous and evoked locomotor activity and (2) on the condition of nigrostriatal projections eight weeks after MG-132 intraperitoneal administration. We also discuss the current status of knowledge about intraperitoneal administration of MG-132, a laboratory method that is being used more and more. Our results revealed a lack of motor abnormalities, but significant loss (20%) of substantia nigra pars compacta dopaminergic neurons after systemic MG-132 administration. This loss was accompanied by a corresponding decrease (8%) of density of dopaminergic terminals in dorsolateral striatum. Moreover, evidence of very limited but ongoing fibre degeneration within the dorsal striatum suggests that MG-132 severely disturbed the nigrostriatal pathway. In summary, intraperitoneal application of proteasome inhibitor MG-132, despite the encouraging results of experimental treatment and prevention of many pathological processes, should be used with caution because of the potential adverse effects on the structure of the central nervous system, especially elements of the nigrostriatal pathway.

The glial cells play an important role in pathophysiology of the intracerebral haemorrhage (ICH). Thus the attempt at evaluating the possible influence of the propofol on the reactivity of astro- and microglial cells in the course of ICH was performed. 50 rats were divided into two groups depending on the applied anaesthesia. All animals were generally anaesthetized with fentanyl, dehydrobenzperidol and midazolam. No additional agents were given to the animals of the control group (group I). In the experimental group (group II), the animals received additionally intraperitoneally propofol in a dose of 50 mg/kg every thirty minutes. ICH was produced through infusion of the blood into the striatum. The astrocytic and microglial cells population was assessed on the 1, 3, 7, 14 and 21 days after producing a haematoma using antibodies anti-GFAP and OX42. The stereological analysis was applied to estimate the numerical density of immunoreactive cells and the distribution of their types. On the 14th and 21st days of observation the density of GFAP-immunoreactivity (ir) cells was significantly higher in group II than that in group I. There were no differences in percentage distribution of GFAP-ir astrocytes between group I and group II. On the 3rd, 14th and 21st days of observation the density of OX42-ir cells was higher in group II in comparison with group I. For the 7th, and 21st days of survival the percentage of the ameboid form of OX42-ir cells was significantly lower in group I than that in group II. The administration of propofol during anaesthesia in the animals with ICH has evoked an increase of the activation of the astro- and microglial cells.

Intracerebral haemorrhage is a strong stimulus for both microglial and astroglial activations. There are some important pathophysiological features during haemorrhage that do not occur in ischaemic or traumatic brain injuries, and may influence the dynamics and intensity of glial activation. Studies on the evolution of glial reaction may have practical importance to the introduction of new therapeutic methods for influencing the inflammatory reaction during haemorrhage. Microglial and astroglial responses to experimental intracerebral haematoma were studied in 50 adult rats for 5 minutes after injection of 100 microl autologous arterial blood into the striatum. The survival period varied from 1 to 21 days. Microglial-macrophage lineage cells were immunocytochemically stained with antibodies OX42, OX6 and ED1. The astrocytic population was studied by means of anti-GFAP staining. Changes in cellular morphology and intensity of staining were time-dependent reactions in both microglial and astroglial cells. Strong activation of microglial-macrophage lineage cells revealed with OX6-and OX42-immunoreactivity started during the first postoperative day. The complete pattern of activation for ED1-immunoreactivity was observed from the third postoperative day. At this stage, numerous phagocytic macrophages started to appear in the perihaematoma region. Morphological changes were most intensive during the second postoperative week. The astroglial (anti-GFAP) reaction was observed after the third postoperative day and proceeded less dynamically. The glial reaction gradually stopped but not completely during the period of observation. The early occurrence of glial activation, pattern of morphological changes and characteristic sequence of antigens expression indicate a very intense type of glial reaction. Evolution of glial response to haemorrhage reveals characteristic features. In our opinion, the initial phase of glial activation, comprising 72 hours after the occurrence of haemorrhage, is potentially the most promising period for influencing the extent of glial reaction with therapeutic agents.

We compared the volumes of the superior temporal gyrus, basolateral temporal area, parahippocampal gyrus, hippocampal head, amygdaloid body and the inferior horn of the lateral ventricle in 29 patients with dementia of Alzheimer's type (DAT) and in 14 cognitively normal controls. Measurements were performed on coronal MR images perpendicular to the long axis of the hippocampus then the raw data were normalised for intracranial volume. The volumes of all studied structures were significantly smaller in patients with DAT than in age-matched control group. The differences in the volume between DAT and age-matched control group were the largest for the amygdaloid body and the basolateral temporal area. The discriminant analysis including the volume of both the basolateral area and the left amygdaloid body allows for correct classification of 100% DAT patients and 93% controls. We conclude that the estimation of the volume of the amygdaloid body and basolateral temporal area seems to be the most important factor for DAT diagnosis.

The experimental model of the intracerebral hematoma in the rabbit was used for the investigation of the changes of the intracranial pressure and selected hemodynamic parameters. The study was performed on 13 adult rabbits, divided into two groups receiving 1 ml (group I--6 animals) and 2 ml (group II--7 animals) of fresh arterial blood, respectively. The monitoring of the intracranial pressure (ICP), the mean arterial blood pressure (MABP), the heart rate (HR), the end-tidal CO2 concentration (ETCO2) and the body temperature was measured every minute in the hematoma production phase and every 5 minutes for the consecutive three hours. The volume of the hematoma was calculated according to Cavalieri formula, with the use of the system for the automatic picture analysis. The mean volume of the intraparenchymal part of the hematoma in group I was higher than in the group II. However, in all the representatives of the second group the evidence of the intraventricular hemorrhage was present. The dynamics of the ICP, MABP and HR changes differed significantly in both groups during the period of the observation. On the basis of the physiological and morphological observations we conclude that the changes of ICP remain the most sensitive and valuable parameter during the early course of the intracerebral hemorrhage. Coexistence of the rapid ICP, MABP and HR changes must be always regarded as the possible sign of the intraventricular hemorrhage.

Microtubules are present in high concentration in the nervous system and are a prominent component of the neuronal cytoskeleton. Microtubules are composed of tubulin and variety of microtubule-associated proteins (MAPs), which have been implicated in the regulation of microtubule assembly and function. MAP2 is the most abundant of these proteins, and it has been extensively characterized in various functional and pathological conditions. In the present study the distribution of MAP2 was examined in each layer of the CA1 and CA3 regions of the hippocampus proper and dentate gyrus in rat development. A total of 40 brains at various ages starting from postnatal day (P) 0 to P90 were examined. After perfusional fixation the brains were frozen and cut on the coronal plane and stained with either cresyl violet or standard immunohistochemical methods using the anti-MAP2 antibody. MAP2 exhibited a somatodendritic pattern of localization in cells of the hippocampus. Staining was most prominent in dendrites and perikarya as well as granules surrounding cell bodies. In a newborn rat's brain immunostaining was intense in granules and faint in perikarya. Between P4 and P21 immunostaining density for MAP2 was stronger and appeared in perikarya, granules, and dendritic trees. After P21 the perikarya and dendrites of the pyramidal layer and stratum radiatum of the hippocampus proper, as well as the molecular and granular layer of dentate gyrus, showed reduced immunoreactivity. In the stratum oriens of the hippocampus and polymorphic layer of the dentate gyrus immunoreactivity was still strong until P90.

Synaptophysin is an integral membrane protein associated with small, electron-lucent synaptic vesicles. Immunohistochemistry for this protein is a sensitive method to study subtle changes in synaptic density and distribution in various brain regions. In the present study, the synaptogenesis was examined in the rat basolateral amygdala in comparison with the hippocampal hilus, from the day of birth to adulthood. A total of 41 brains at various ages starting from P0 to P90 (P--postnatal day) were examined. After perfusional fixation the brains were frozen and cut in the coronal plane and stained either with cresyl violet or standard immunohistochemical methods using the anti-synaptophysin antibody. Synaptophysin positive granules appeared just after birth in both structures, but their number was very low (about 0.28 x 10(6) and 0.13 x 10(6) per mm3 in the amygdala and hippocampus, respectively). In the basolateral amygdala the number of synapses increased rapidly reaching the maximum at P14 (1.6 x 10(6) per mm3) followed by about 45% decrease in number up to P30 and later being stabile. In the hippocampus two increases of the synaptogenesis were observed. The first at P7 (about 1.7 x 10(6) of synapses per 1 mm3) which was followed by dramatic decrease up to 0.7 x 10(6) per mm3 at P14. The second increase appeared later (about P90) and reached 1.7 x 10(6) per mm3. After that time the density of synapses was stabile. It may be supposed that the first characteristic wave of synaptogenesis observed in the hippocampus and amygdaloid body is due to the overproduction of synapses observed at that time in other cortical regions. The late wave of synaptogenesis found in the hippocampus is related to the great plasticity of the interneuronal connections in this period of development.

The thalamic reticular nucleus (Rt) is a thin lamina of cells, through which thalamocortical and corticothalamic fibers pass. It is interposed between the thalamic nuclei and the internal capsule and it is composed of GABA-ergic cells with synapses that receive impulses from both kinds of fibers. Rt takes part in the negative feed-back system of controlling the information transfer from the thalamus to the cerebral cortex and it is focused in the sleep-waking cycle. The pattern of parvalbumin reactivity during maturation of Rt becomes the main aim of our study. The study was performed on 36 rats on various postnatal days (P0, P1, P2, P4, P5, P7, P10, P14, P17, P21, P30 and P90). The animals were anesthetized, transcardially perfused, cut on cryostat into 30-microns-thick frontal sections, stained immunocytochemically using standard ABC method and a mouse monoclonal antibody against parvalbumin. A small amount of round and oval, parvalbumin immunopositive cells was detected at stage PO, predominantly in the intermediate part of Rt, whereas the cells in ventral and lateral part at the same time were only slightly immunopositive. At P10 the cells in the intermediate part became more fusiform or oval because of the appearance of dendrites. At P14 we were able to observe separate, punctuated structures interpreted as the axonal endings. There were plenty of them at the time of full maturation of the intermediate portion of reticular nucleus (stage P21). At this time, the dorsal and ventral parts had their first synapses, too, but their maturation ended a week later. At P30 multipolar neurons, with round and fusiform somata were distributed relatively homogeneously throughout Rt. We compared the stage with the parvalbumin reactivity of the adult rat and found no difference in the morphological pattern of PV neurons.

The study was performed on 19 brains of nondemented patients with age ranging from 36 to 89 years. After embedding in paraffin, coronal 8-microns-thick serial sections were cut and stained either with cresyl violet or with immunocytochemical methods for amyloid and tangles. Morphometrical studies were performed in all parts of the claustrum along its whole extension. Changes related to aging (neuronal loss and decrease in volume) were found in all parts of the claustrum, but the time of origin of these changes is different in various parts of this structure. We did not observe neurofibrillary pathology in any parts of the claustrum. In the oldest subjects a small number of amyloid plaques was found in the paraamygdalar part of the claustrum. We suggest that the neurons of the claustroneocortical loop are affected severely and earlier than those in the claustroentorhinal loop.

The involvement of the claustrum in processing of somatosensory information was investigated using the formalin test as an established pain test. The metabolic activity of the claustrum and other brain structures belonging to the somatosensory system was assessed by autoradiographic method of the uptake of (3H)-labelled 2-deoxyglucose (2-DG). Glucose utilization in the claustrum was stimulated by subcutaneous injection of formalin into the front paw. The increase of radioactivity was observed not only in the claustrum, but also in the anterior pretectum, the ventral thalamic nucleus, the somatosensory, insular and piriform cortices on the contralateral side to formalin stimulation. After stereotactical injection of morphine into the contralateral pretectum to stimulation side, uptake of 2-DG in the claustrum was abolished. These results indicate that the claustrum is an important relay nucleus in the somatosensory system, which may convey somatosensory information from the pretectum to the cerebral cortex, thus by-passing the thalamus, throughout the pretecto-claustro-cortical pathways.

Methylazoxymethanol acetate (MAM) is a substance that inhibits migration of neurons in the embryonic brain. After intraperitoneal injection of two different doses of MAM to pregnant rats, microcephaly with or without complete development of the cerebral cortex was observed in every litter. High MAM doses (30 mg/kg) resulted in the lack of superficial layers (II-IV) of the cerebral cortex when the deep layers (V, VI) were seen. The claustrum was present but composed of loosely packed, medium-size, triangular or fusiform neurons with anarchic oriented long axes. After administration of low MAM doses (14 mg/kg) two different parts (medial and lateral) of the insular claustrum were observed. Our results suggest that neurons of the insular claustrum create two different subpopulations of cells, which were similar to that observed in primitive insectivore (e.g., hedgehog), but fuse in development.