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Acute ischemic stroke results in an ischemic core surrounded by a tissue at risk, named the penumbra, which is potentially salvageable. One way to differentiate the tissues is to measure the hypoxia status. The purpose of the current study is to correlate the abnormal brain tissue volume derived from magnetic resonance-based imaging of brain oxygen saturation (S

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Background: Cerebrospinal fluid (CSF) diversion by shunts is the most common surgical treatment for hydrocephalus. Though effective, shunts are associated with risk of dysfunction leading to multiple surgical revisions, affecting patient quality-of-life and incurring high healthcare costs. There is a need for ambulatory monitoring systems for life-long assessment of shunt status. The present study aimed to develop a preclinical model assessing the feasibility of our wireless device for continuous monitoring of cerebral pressure in shunts. Methods: We first adapted a previous hydrocephalus model in sheep, which used an intracisternal kaolin injection. Seven animals were used to establish the model, and 1 sheep with naturally dilated ventricles was used as control. Hydrocephalus was confirmed by clinical examination and brain imaging before inserting the ventriculoperitoneal shunts and the monitoring device allowing continuous measurement of the pressure through the shunt for a few days in 3 sheep. An external ventricular drain was used as gold-standard. Results: Our results showed that a reduction in kaolin dose associated to postoperative management was crucial to reduce morbidity and mortality rates in the model. Ventriculomegaly was confirmed by imaging 4 days after injection of 75 mg kaolin into the cisterna magna. For the implanted sheep, recordings revealed high sensitivity of our sensor in detecting fluctuations in cerebral pressure compared to conventional measurements. Conclusions: This proof-of-concept study highlights the potential of this preclinical model for testing new shunt devices.

It was previously reported that normobaric oxygen therapy (NBO) significantly affected T2∗-weighted imaging in a mouse model of intracerebral hemorrhage (ICH). However, it is unclear whether a similar phenomenon exists in large volume ICH as seen in human pathology. We investigated the effects of NBO on T2∗-weighted images in a pig model of ICH. Our data show that NBO makes disappear a peripheral crown of the hematoma, which in turn decreases the apparent volume of ICH by 18%. We hypothesized that this result could be translated to ICH in human, and subsequently could lead to inaccurate diagnostic.

Although chronic arterial hypertension (CAH) represents the major comorbid factor in stroke, it is rarely integrated in preclinical studies of stroke. The majority of those investigations employ spontaneously hypertensive rats (SHR) which display a susceptibility to ischemic damage independent of hypertension. Here, we used a renovascular model of hypertension (RH) to examine, with magnetic resonance imaging (MRI), brain alterations during the development of hypertension and after brain ischemia. We also examined whether MRI-derived parameters predict the extent of ischemia-induced brain damage. RH was induced according to the two-kidney one-clip model and multiparametric MRI was performed at 3, 6, 9, and 12 weeks after hypertension and also at 10, 50, and 60 min following stroke. Blood pressure values increased progressively and reached a plateau at 6 weeks after RH induction. At 12 weeks, all hypertensive animals displayed spontaneous brain lesions (hemorrhages, deep and cortical lesions, ventricular dilatation), increased apparent diffusion coefficient (ADC) values in the corpus callosum and higher fractional anisotropy in the cortex. Following ischemia, these animals showed larger brain lesions (406 ± 82 vs. 179 ± 36 mm3, p

Background Brain metastases (BM) develop frequently in patients with breast cancer. Despite the use of external beam radiotherapy (EBRT), the average overall survival is short (6 months from diagnosis). The therapeutic challenge is to deliver molecularly targeted therapy at an early stage when relatively few metastatic tumor cells have invaded the brain. Vascular cell adhesion molecule 1 (VCAM-1), overexpressed by nearby endothelial cells during the early stages of BM development, is a promising target. The aim of this study was to investigate the therapeutic value of targeted alpha-particle radiotherapy, combining lead-212 (212Pb) with an anti–VCAM-1 antibody (212Pb-αVCAM-1). Methods Human breast carcinoma cells that metastasize to the brain, MDA-231-Br-GFP, were injected into the left cardiac ventricle of nude mice. Twenty-one days after injection, 212Pb-αVCAM-1 uptake in early BM was determined in a biodistribution study and systemic/brain toxicity was evaluated. Therapeutic efficacy was assessed using MR imaging and histology. Overall survival after 212Pb-αVCAM-1 treatment was compared with that observed after standard EBRT. Results 212Pb-αVCAM-1 was taken up into early BM with a tumor/healthy brain dose deposition ratio of 6 (5.52e108 and 0.92e108) disintegrations per gram of BM and healthy tissue, respectively. MRI analyses showed a statistically significant reduction in metastatic burden after 212Pb-αVCAM-1 treatment compared with EBRT (P < 0.001), translating to an increase in overall survival of 29% at 40 days post prescription (P < 0.01). No major toxicity was observed. Conclusions The present investigation demonstrates that 212Pb-αVCAM-1 specifically accumulates at sites of early BM causing tumor growth inhibition.

It was previously reported that normobaric oxygen therapy (NBO) significantly affected T2

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Recent data have shown that normobaric oxygen (NBO) increases the catalytic and thrombolytic efficiency of recombinant tissue plasminogen activator (rtPA) in vitro, and is as efficient as rtPA at restoring cerebral blood flow in rats subjected to thromboembolic brain ischemia. Therefore, in the present study, we studied the effects of hyperbaric oxygen (HBO) (i) on rtPA-induced thrombolysis in vitro and (ii) in rats subjected to thromboembolic middle cerebral artery occlusion-induced brain ischemia. HBO increases rtPA-induced thrombolysis in vitro to a greater extent than NBO; in addition, HBO treatment of 5-minute duration, but not of 25-minute duration, reduces brain damage and edema in vivo. In line with the facilitating effect of NBO on cerebral blood flow, our findings suggest that 5-minute HBO could have provided neuroprotection by promoting thrombolysis. The lack of effect of HBO exposure of longer duration is discussed.

International audience; Recent data have shown that normobaric oxygen (NBO) increases the catalytic and thrombolytic efficiency of recombinant tissue plasminogen activator (rtPA) in vitro, and is as efficient as rtPA at restoring cerebral blood flow in rats subjected to thromboembolic brain ischemia. Therefore, in the present study, we studied the effects of hyperbaric oxygen (HBO) (i) on rtPA-induced thrombolysis in vitro and (ii) in rats subjected to thromboembolic middle cerebral artery occlusion-induced brain ischemia. HBO increases rtPA-induced thrombolysis in vitro to a greater extent than NBO; in addition, HBO treatment of 5-minute duration, but not of 25-minute duration, reduces brain damage and edema in vivo. In line with the facilitating effect of NBO on cerebral blood flow, our findings suggest that 5-minute HBO could have provided neuroprotection by promoting thrombolysis. The lack of effect of HBO exposure of longer duration is discussed.

Background: The lack of a relevant stroke model in large nonhuman primates hinders the development of innova- tive diagnostic/therapeutic approaches concerned with this cerebrovascular disease. Our objective was to develop a novel and clinically relevant model of embolic stroke in the anesthetized monkey that incorporates readily available clinical imaging techniques and that would allow the possibility of drug delivery including strategies of reperfusion. Methods: Thrombin was injected into the lumen of the middle cere- bral artery (MCA) in 12 anesthetized (sevoflurane) male rhesus macaques (Macaca mulatta). Sequential MRI studies (including angiography, FLAIR, PWI, DWI, and gadolinium-enhanced T1W imaging) were performed in a 3T clinical MRI. Physiological and biochemical parameters were monitored throughout the investigations. Results: Once standardized, the surgical procedure induced transient occlusion of the middle cerebral artery in all operated animals. All animals studied showed spontaneous reperfusion, which occurred some time between 2 h and 7 days post-ictus. Eighty percent of the studied animals showed diffusion/perfusion mismatch. The ischemic lesions at 24 h spared both superficial and profound territories of the MCA. Some animals presented hemorrhagic transformation at 7 days post-ictus. Conclusion: In this study, we developed a pre-clinically relevant model of embolic stroke in the anesthetized nonhuman primate.

During the past decade, studies on the manipulation of various inhaled inert gases during ischemia and/or reperfusion have led to the conclusion that inert gases may be promising agents for treating acute ischemic stroke and perinatal hypoxia-ischemia insults. Although there is a general consensus that among these gases xenon is a golden standard, the possible widespread clinical use of xenon experiences major obstacles, namely its availability and cost of production. Interestingly, recent findings have shown that helium, which is a cost-efficient inert gas with no anesthetic properties, can provide neuroprotection against acute ischemic stroke in vivo when administered during ischemia and early reperfusion. We have investigated whether helium provides neuroprotection in rats subjected to middle cerebral artery occlusion (MCAO) when administered after reperfusion, a condition prerequisite for the therapeutic viability and possible clinical use of helium. In this study, we show that helium at 75 vol% produces neuroprotection and improvement of neurologic outcome in rats subjected to transient MCAO by producing hypothermia on account of its high specific heat as compared with air.

Brain insults are a major cause of acute mortality and chronic morbidity. Given the largely ineffective current therapeutic strategies, the development of new and efficient therapeutic interventions is clearly needed. A series of previous investigations has shown that the noble and anesthetic gas xenon, which has low-affinity antagonistic properties at the N-methyl-D-aspartate (NMDA) receptor, also exhibits potentially neuroprotective properties with no proven adverse side effects. Surprisingly and in contrast with most drugs that are being developed as therapeutic agents, the dose-response neuroprotective effect of xenon has been poorly studied, although this effect could be of major critical importance for its clinical development as a neuroprotectant. Here we show, using ex vivo and in vivo models of excitotoxic insults and transient brain ischemia, that xenon, administered at subanesthetic doses, offers global neuroprotection from reduction of neurotransmitter release induced by ischemia, a critical event known to be involved in excitotoxicity, to reduction of subsequent cell injury and neuronal death. Maximal neuroprotection was obtained with xenon at 50 vol%, a concentration at which xenon further exhibited significant neuroprotective effects in vivo even when administered up to 4 h after intrastriatal NMDA injection and up to at least 2 h after induction of transient brain ischemia.

Background and Purpose— Whereas the effects of chronic arterial hypertension on the cerebral vasculature have been widely studied, its effects on brain tissue have been studied less so. Here we examined if spontaneously hypertensive rats (SHRs) or the normotensive control Wistar Kyoto rats (WKYs) made hypertensive by renal artery stenosis (R-WKYs) are vulnerable to an excitotoxic brain lesion provoked by an overactivation of glutamate receptors. Methods— Lesion volumes were quantified by histology in WKYs and SHRs subjected to striatal administration of N -methyl- d -aspartate (NMDA) or α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA). The expression of AMPA receptors subunits and calcium/calmodulin kinase-IIα was analyzed by real-time polymerase chain reaction and Western blot. Results— NMDA (50 and 75 nmol) induced similar lesions in both SHRs (10±2 mm 3 and 16±4 mm 3 , respectively) and WKYs (11±2 mm 3 and 19±7 mm 3 , respectively). However, AMPA-induced (2.5 and 5 nmol) lesions were significantly greater in 14-week-old SHRs (14±3 mm 3 and 20±5 mm 3 , respectively) than WKYs (4±2 mm 3 , P 3 , P 3 vs 6±3 mm 3 ; P 3 and 5±4 mm 3 , respectively) compared with WKYs. Striatal levels of AMPA receptors subunits, GluR1 and GluR2, were not different between SHRs and WKYs. However, SHRs displayed an increase in phosphorylated form of GluR1 at Ser-831 ( P P P Conclusions— These findings show that an increase in phosphorylated GluR1, which increases AMPA receptor conductance, may be involved in the vulnerability of SHRs to AMPA.

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The mechanisms underlying functional recovery after stroke are poorly understood. Brain-adaptive responses to the hypoxic stress elicited by ischemia could contribute to these mechanisms. Indeed, hypoxia-inducible factor-1 (HIF-1), one of the main transcriptional factors regulated by oxygen level, increases the expression of several beneficial genes such as erythropoietin, glucose transporter-1 and vascular endothelial growth factor. In order to strengthen the expression of these hypoxia-inducible factors, we administered deferoxamine, an iron chelator known to stabilize HIF-1alpha protein expression, and examined its effects on the functional deficits induced by ischemia. Anesthetized Sprague-Dawley rats were subjected to 60 min of intraluminal occlusion of the middle cerebral artery. Chronic deferoxamine treatment (300 mg/kg, s.c.), or its vehicle, started 24 h after ischemia and was continued bi-weekly until the animals were killed. Sensorimotor deficits were periodically assessed over 2 months, and at this end point, the lesion volume was determined by histology. Treatment with deferoxamine significantly decreased the size of brain damage (-28%) after ischemia and improved behavioral recovery. Indeed, neurological score and sensorimotor performances in the adhesive removal test recovered earlier in the deferoxamine-treated animals. Moreover, the long-lasting skilled forepaw reaching deficits were attenuated by deferoxamine. Although an antioxidant effect of deferoxamine cannot be excluded, the hypothesis that its beneficial effects could be mediated by an increase in HIF-1 target genes merits further investigations. Our data suggest that delayed administration of deferoxamine could represent an interesting therapeutical approach to treat focal cerebral ischemia.

International audience; Normobaric oxygen (NBO) and hyperbaric oxygen (HBO) are emerging as a possible co-treatment of acute ischemic stroke. Both have been shown to reduce infarct volume, to improve neurologic outcome, to promote endogenous tissue plasminogen activator-induced thrombolysis and cerebral blood flow, and to improve tissue oxygenation through oxygen diffusion in the ischemic areas, thereby questioning the interest of HBO compared to NBO. In the present study, in order to investigate and compare the oxygen diffusion effects of NBO and HBO on acute ischemic stroke independently of their effects at the vascular level, we used acute brain slices exposed to oxygen and glucose deprivation, an ex vivo model of brain ischemia that allows investigating the acute effects of NBO (partial pressure of oxygen (pO2) = 1 atmospheres absolute (ATA) = 0.1 MPa) and HBO (pO2 = 2.5 ATA = 0.25 MPa) through tissue oxygenation on ischemia-induced cell injury as measured by the release of lactate dehydrogenase. We found that HBO, but not NBO, reduced oxygen and glucose deprivation-induced cell injury, indicating that passive tissue oxygenation (i.e. without vascular support) of the brain parenchyma requires oxygen partial pressure higher than 1 ATA.

SummaryBackgroundMultidetector computed tomography (MDCT) provides a non-invasive anatomic description of the coronary veins that may be useful in patients candidates to cardiac resynchronization. Prospective gating reduces radiation exposure but its impact on image quality is unknown is this setting.AimsThis study compared image quality and reliability of MDCT angiography of the coronary veins between prospective and retrospective gating.MethodsSeven anaesthetized pigs underwent 64-detector row MDCT with prospective and retrospective ECG-gating. MDCT scans were evaluated for visibility of the veins, estimated radiation dose and vein characteristics. Inter- and intra-observer reproducibility was calculated.ResultsVisibility grades of all veins were significantly decreased in prospective (0.82±0.6) compared to retrospective gating (1.68±0.9; P

The lack of a relevant stroke model in large nonhuman primates hinders the development of innovative diagnostic/therapeutic approaches concerned with this cerebrovascular disease. Our objective was to develop a novel and clinically relevant model of embolic stroke in the anesthetized monkey that incorporates readily available clinical imaging techniques and that would allow the possibility of drug delivery including strategies of reperfusion.Thrombin was injected into the lumen of the middle cerebral artery (MCA) in 12 anesthetized (sevoflurane) male rhesus macaques (Macaca mulatta). Sequential MRI studies (including angiography, FLAIR, PWI, DWI, and gadolinium-enhanced T1W imaging) were performed in a 3T clinical MRI. Physiological and biochemical parameters were monitored throughout the investigations.Once standardized, the surgical procedure induced transient occlusion of the middle cerebral artery in all operated animals. All animals studied showed spontaneous reperfusion, which occurred some time between 2 h and 7 days post-ictus. Eighty percent of the studied animals showed diffusion/perfusion mismatch. The ischemic lesions at 24 h spared both superficial and profound territories of the MCA. Some animals presented hemorrhagic transformation at 7 days post-ictus.In this study, we developed a pre-clinically relevant model of embolic stroke in the anesthetized nonhuman primate.

Neurokinins (NKs) are the most important of the peptides released from neuronal sensory afferents. In mammals different NKs [substance P (SP), neurokinin A (NKA) and neurokinin B (NKB)] act as neurotransmitters and neuromodulators.(1) The biological responses induced by these neuropeptides are mediated by three distinct receptors NK1, NK2 and NK3 respectively. The NK1 receptors are widely distributed throughout the CNS and peripheral nervous systems. In recent years, clinical studies with selective NK1 receptor antagonists showed results for the treatment of emesis, depression, anxiety, pain and migraine.(2) Since the discovery of the first selective non-peptide NK1 antagonist CP-96,345, a considerable research in this area has been developed by the pharmaceutical industry.(3) In 1995, Takeda company described a novel class of highly potent, selective, and orally active NK1 antagonists such as 6-pyrido[3, 4-b]pyridinecarboxamide derivatives.(4) In this series, EP 00652218 1 (Scheme 1) was shown to exhibit subnanomolar affinity (IC50: 0.21nM, in vitro inhibition of [125I]-BH-SP binding in human IM-9 cells) towards the NK1 receptors. Moreover, SAR studies demonstrated that the bis (trifluoromethylbenzyl) moiety was essential for the affinity. This led us to consider that EP 00652218 1 could be a good candidate for in vivo imaging of NK1 receptors and that the design of pyridine or phenyl ring substituted analogs would retain a high affinity. In order to develop ligands that could be used either in PET or SPECT studies, we undertook the synthesis of compounds bearing an halogen atom (fluorine, bromine or iodine). In this paper we report both the synthesis and labelling of the reference EP 00652218 1 with carbon-11 and of the analog 2 with fluorine-18 (Schemes 1, 2 and 3).

International audience; Distal occlusion of the middle cerebral artery (dMCAo), which closely mimics human stroke, is one of the most used animal models. However, although assessment of histological and functional outcome is increasingly recommended for preclinical studies, the latter is often excluded because of the high difficulties to estimate, especially in mice, behavioral impairments. The aim of our study was to deeply screen functional consequences of distal permanent MCAo in mice to target relevant behaviors for future studies. A set of sensorimotor and cognitive tests were performed during 3 weeks postsurgery in 2 groups of mice. Afterward, brain infarctions were estimated by histological staining or magnetic resonance imaging. Overall, while no long-term functional impairments could be detected, the adhesive removal was the only test showing a deficit. Interestingly, this sensorimotor impairment was correlated to cortical damage 3 weeks after surgery. In conclusion, despite the fact that dMCAo-induced deficits could not be evidenced by most of our behavioral tests, the authors showed that the adhesive removal test was the only one, sensitive enough, to highlight a long-term deficit. This result suggests therefore that this mouse model of ischemia is relevant to efficiently assess therapeutic strategies with histological but also behavioral analysis, provided that relevant tests are used.

BACKGROUND AND OBJECTIVE: Preliminary studies have shown that nitrous oxide, like xenon, may possess potentially neuroprotective properties. However, because of its possible neurotoxic and proneurotoxic effects (obtained under particular conditions) and its bad reputation at anesthetic concentrations, no thorough investigations have been performed on the potentially neuroprotective properties of nitrous oxide. The aim of this study was to investigate the possible neuroprotective effects of nitrous oxide at nonanesthetic concentrations on different models of excitotoxic insult and brain ischemia. MEASUREMENTS AND MAIN RESULTS: Here, we show using multiple models of ex vivo and in vivo excitotoxic insults and brain ischemia that nitrous oxide, administered alone at nonanesthetic doses, offers global neuroprotection from reduction of neurotransmitter release induced by ischemia to reduction of subsequent cell injury. In vivo, in rats subjected to transient cerebral ischemia, nitrous oxide at 50 vol% offers full neuroprotection at both the histologic and neurologic outcome levels when administered up to 2 hrs, but not 3 hrs, after ischemia onset. CONCLUSIONS: These data provide experimental evidence that nitrous oxide, which is a cost-efficient and easily available gas, has potentially neuroprotective properties in rodents when given alone at nonanesthetic concentrations. Therefore, because there is a lot at stake for the affected patients and society--in terms of easy access to treatment, profound impact of brain damage, cost of treatment, and subsequent financial cost on society--we believe that further studies should investigate thoroughly the possible potential clinical interest of nitrous oxide for the treatment of ischemic stroke in terms of optimal indications, type of ischemic injury, duration and time points for treatment, and the optimal concentration of gas to be used in clinical circumstances.

International audience; Urotensin-II (U-II) is a cyclic peptide identified recently in many mammalian species including man. U-II and its receptor are expressed in the central nervous system, in the cardiovascular system and in other peripheral tissues. Although this peptide has been reported initially to be a potent vasoconstrictor, increasing evidence shows that its vascular actions strongly depend on species and vascular beds. Here we analyzed the effects of U-II administration on cerebral blood flow (CBF) under physiological conditions and following cerebral ischemia in rats. Although intravenous injection of U-II had minimal effects on CBF as measured by the technique of laser Doppler flowmetry, its administration (10 nmol) into the lateral cerebral ventricle induced gradual and long lasting increase in CBF (+61% at 1 h post-injection, p

Mecamylamine is a well-described non specific antagonist of nicotinic acetylcholine receptors (nAChRs), used in therapy and in psychopharmacological studies. [ 11 C]-Mecamylamine was prepared and evaluated as a putative radioligand for positron emission tomography to study nicotinic acetylcholine receptors. The radiosynthesis consisted in the [ 11 C]-methylation of the desmethyl precursor within 40 min with 30–40% radiochemical yield decay corrected. Biodistribution studies in rats showed that radioligand crossed the blood-brain barrier (0.39% ID at 30 min) and only unmetabolized tracer was recovered from brain at 45 min. Ex vivo autoradiography studies in rats did not indicate preferential uptake, and pre-treatment mecamylamine or with chlorisondamine, an nicotinic receptor inhibitor, did not demonstrate a significant specific binding. To investigate possible specie differences and effects of anesthesia, in vivo positron emission tomography (PET) studies were carried out on anaesthetized baboons and conscious macaques. The regional brain distribution of [ 11 C]-mecamylamine in the two species of primates exhibited similar kinetics as did the rat with steady state reached about 45–50 min after radiotracer administration. Uptake values were two-fold higher in brain of conscious macaque than in anaesthetized baboon (thalamus: 0.258% ID/(kg mL) in conscious macaques and 0.129% ID/(kg mL) in baboons). PET images showed a radioactivity distribution which was quite homogeneous throughout the brain but with somewhat higher uptake in grey matter than in white. Brain distribution was unaltered by saturation or displacement studies. Possible explanation for the failure to establish specific binding in vivo could be long-lived structural modifications of the ionotropic channel by the unlabeled ligand administered before the tracer. In conclusion, [ 11 C]-mecamylamine did not satisfy the requirements for a PET tracer of nicotinic acetylcholine receptors.

Neuronal death after ischemia-induced brain damage depends largely upon the activation of the N-methyl-D-aspartate (NMDA) excitatory glutamate receptor that is a target for many putative neuroprotective agents. Whereas the NMDA receptors mediate ischemic brain damage, blocking them is deleterious in humans. Here, the authors investigated whether nitrous oxide or xenon, which are gaseous anesthetics with a remarkably safe clinical profile that have been recently demonstrated as effective inhibitors of the NMDA receptor, may reduce the following: (1) ischemia-induced brain damage in vivo, when given after occlusion of the middle cerebral artery (MCAO), a condition needed to make these potentially neuroprotective agents therapeutically valuable; or (2) NMDA-induced Ca2+ influx in cortical cell cultures, a major critical event involved in excitotoxic neuronal death. The authors have shown that both nitrous oxide at 75 vol% and xenon at 50 vol% reduce ischemic neuronal death in the cortex by 70% and further decrease NMDA-induced Ca2+ influx by 30%. In addition, xenon at 50%, but not nitrous oxide at 75 vol%, further decreases ischemic brain damage in the striatum (a subcortical structure that is known to be resistant to neuroprotective interventions). However, at a higher concentration (75 vol%), xenon exhibits potentially neurotoxic effects. The mechanisms of the neuroprotective and potentially neurotoxic effects of nitrous oxide and xenon, as well as the possible therapeutic implications in humans, are discussed.

There has been an increasing interest in recent years in the evaluation of the neuronal and glial responses to ischemic insult. Some cytokines, including transforming growth factor-β (TGF-β), that are overexpressed after experimental stroke in rodents are thought to be implicated in the neuronal processes that lead to necrosis. Thus, such cytokines could predict tissue fate after stroke in humans, although data are currently sparse for gyrencephalic species. The current study addressed the expression pattern of TGF-β1 in a nonhuman primate model of middle cerebral artery occlusion. Focal permanent ischemia was induced for 1 or 7 days in 6 baboons and the following investigations were undertaken: cerebral oxygen metabolism (CMRO2) positron emission tomography studies, magnetic resonance imaging, postmortem histology, and reverse transcription-polymerase chain reaction. The aim of the current study was to correlate the expression of TGF-β1 to the underlying metabolic and histologic state of the threatened cerebral parenchyma. The authors evidenced increased TGF-β1 mRNA levels (up to 25-fold) in those regions displaying a moderate (20% to 49%) reduction in CMRO2. The current findings suggest that the greatly enhanced expression of TGF-β1 in the penumbral zones that surround tissue destined to infarction may represent a robust index of potentially salvageable brain. The current investigation, in the nonhuman primate, strengthens the authors' hypothesis, derived from rodent models, that TGF-β1 may be involved in the physiopathology of human stroke.

Background The use and benefits of normobaric oxygen (NBO) in patients suffering acute ischemic stroke is still controversial. Results Here we show for the first time to the best of our knowledge that NBO reduces both NMDA-induced calcium influxes in vitro and NMDA-induced neuronal degeneration in vivo, but increases oxygen and glucose deprivation-induced cell injury in vitro and ischemia-induced brain damage produced by middle cerebral artery occlusion in vivo. Conclusions Taken together, these results indicate that NBO reduces excitotoxin-induced calcium influx and subsequent neuronal degeneration but favors ischemia-induced brain damage and neuronal death. These findings highlight the complexity of the mechanisms involved by the use of NBO in patients suffering acute ischemic stroke.