Ischemic Brain Damage In Rats Research Articles

Experience of using intracranial introduction of endothelin-1 for inducing ischemic brain damage in rats to evaluate cell therapy efficacy

Experience of using intracranial introduction of endothelin-1 for inducing ischemic brain damage in rats to evaluate cell therapy efficacy

Accelerated Method for Determining Ischemic Brain Damage in Rats and Assessment the Neuroprotective Effect of a Complex Herbal Remedy.

The severity of ischemic injury was evaluated by densitometry of brain samples stained with 2,3,5-triphenyltetrazolium chloride (TTC) on a rat model of cerebral ischemia/reperfusion (common carotid artery occlusion) and the neuroprotective activity of an extract of Astragalus membranaceus, Scutellaria baicalensis, and Phlojodicarpus sibiricus was assessed. Occlusion of the common carotid arteries led to a weakening of TTC staining of the brain tissue: densitometric indicators of the staining intensity for the cortex and striatum were lower than the corresponding indicators of sham-operated rats by 18.3 and 10.4%. The mean intensity of staining of brain samples did not differ in rats treated with the extract and sham-operated animals, which attested to its neuroprotective effect. The applied method is convenient for evaluation of the severity of ischemic brain damage at the early stages and screening potential neuroprotective agents.

Silencing miRNA-324-3p protects against cerebral ischemic injury via regulation of the GATA2/A1R axis.

Previous studies have suggested that miR-324-3p is related to the pathophysiology of cerebral ischemia, but the mechanism underlying this relationship is unclear. In this study, we found that miR-324-3p expression was decreased in patients with acute ischemic stroke and in in vitro and in vivo models of ischemic stroke. miR-324-3p agomir potentiated ischemic brain damage in rats subjected to middle cerebral artery occlusion, as indicated by increased infarct volumes and cell apoptosis rates and greater neurological deficits. In a PC12 cell oxygen-glucose deprivation/reoxygenation model, a miR-324-3p mimic decreased cell viability and expression of the anti-apoptotic protein BCL2 and increased expression of the pro-apoptotic protein BAX and rates of cell apoptosis, whereas treatment with a miR-324-3p inhibitor had the opposite effects. Silencing miR-324-3p increased adenosine A1 receptor (A1R) expression through regulation of GATA binding protein 2 (GATA2). These findings suggest that silencing miR-324-3p reduces ischemic brain damage via the GATA2/A1R axis.

Characteristics of nervous tissue after modeling of focal cerebral ischemia in rats at different periods of reperfusion

The stroke-causing problems are extremely important in Ukraine. This makes a heavy burden not only on the health care system, but also on the whole society as a whole. That's why we've studied structural and ultrastructural changes of cortical neurons and striatum of the brain and the development of delayed death of nerve cells after the modeling of the middle cerebral artery occlusion (MCAO) and post ischemic period in rats. We've analyzed the data at different terms after modeling of MCAO. The purpose of the study was to investigate the changes in the nervous tissue in the modeling of focal cerebral ischemia by monofilament occlusion of MCAO in rats at different periods of reperfusion. The statistical processing of primary digital experimental data was carried out using the software Statistica 6.0. It was confirmed that the 60-minute occlusion of the MCAO is an adequate model of focal ischemic brain damage in rats. Changes of locomotor activity and a tactile sensitivity were determined in rats after occlusion and after reperfusion during the post-period period. It was found that in the experimental group with a reperfusion period of 72 hours, a clear increase of the volume of the ischemic area of the brain, accompanied by significant neurological deficiency, was observed. Reduced research activity of the rats was revealed, which was shown in the decrease of the number of squares they crossed, the number of racks, the increase of acts of grooming and the duration of acts of frizings. Following ischemic brain damage, there was also a disbalance of somato-sensory functions, as evidenced by an increase in the time during which the animal took a test stimulus ("Sticky tape") from both the anterior paws when tested for tactile sensitivity (adhesive removal test). An electron microscopic study of the cortex showed that dark wrinkled neurons and enlightened swollen neurons were observed at 72 hours of post-occlusion period, indicating different ways of death of these cells. Changes in striatum were similar to changes in the cortex, which progressed with an increase in the post-occlusion period. The protocol of the serial evaluation of neurological disorders used after MCAO modeling allowed detecting long-term stable functional disorders in laboratory rats. The obtained data indicate significant changes in the structure of the cortex and striatum in the post-ischemic period and the progressive nature of these changes.

Future perspectives of cell therapy for neonatal hypoxic-ischemic encephalopathy.

Neonatal ischemic brain injury causes permanent motor-deficit cerebral palsy. Hypoxic-ischemic encephalopathy (HIE) is a very serious condition that can result in death and disability. In 1997, we reported that irreversible neuronal cell damage is induced by the elevation of intracellular Ca ion concentration that has occurred in sequence after excess accumulation of the excitatory neurotransmitter glutamate during ischemia. We also reported that hypothermia was effective in treating ischemic brain damage in rats by suppressing energy loss and raising intracellular Ca ion concentration. Following the 2010 revised International Liaison Committee on Resuscitation guideline, our group developed the Guideline for the treatment of Hypothermia in Japan, and we started online case registry in January 2012. However, therapeutic hypothermia must be initiated within the first 6 h after birth. By contrast, cell therapy may have a much longer therapeutic time window because it might reduce apoptosis/oxidative stress and enhance the regenerative process. In 2014, we administered autologous umbilical cord blood stem cell (UCBC) therapy for neonatal HIE, for the first time in Japan. We enrolled five full-term newborns with moderate-to-severe HIE. Our autologous UCBC therapy is leading to new protocols for the prevention of ischemic brain damage.

Intravenous Infusion of Ginsenoside Rb1 Ameliorates Compressive Spinal Cord Injury through Upregulation of Bcl-xL and VEGF

Background: Red ginseng root (Panax Ginseng C.A. Meyer) has been used clinically by many Asian people for thousands of years without any detrimental effects. One of the major components of red ginseng root is ginsenoside Rb1 (gRb1, C54H92O23, molecular weight 1109.46). Previously, we showed that intravenous infusion of gRb1 attenuated ischemic brain damage in rats through up-regulation of an anti-apoptotic factor, Bcl-xL. In the present study, we have investigated whether intravenous infusion of gRb1attenuates spinal cord injury or not. Methods: Adult male Wistar rats aged 12-14 weeks, weighing 250-300g, were used. Spinal cord injury (SCI) was induced by compressing the thoracic cord (Th12) with a 20 g weight for 20 minutes. Thirty minutes later, a total of 60µl gRb1 solution (12 or 60µg/60µl in saline) or the same volume of vehicle (saline) was infused once into the left femoral vein. Subsequently, continuous intravenous administration of gRb1 was performed for 7 days. The locomotor function was assessed using the Basso-BeattieBresnahan (BBB) score and the open field test at 1, 3 or 7days after SCI. The animals were killed at 7 days after SCI and the SCI lesions were assessed histologically. Results: Post-traumatic intravenous infusion of gRb1 (12µg/day or 60µg/day) ameliorated BBB score, rearing activity and neuronal density in the anterior horn of the damaged spinal cord at 7 days after SCI. Subsequent studies that focused on gRb1-induced expression of gene products responsible for neuronal death or survival revealed that gRb1 upregulated the expression of not only Bcl-x L , but also a potent angiogenic and neurotrophic factor, vascular endothelial growth factor (VEGF) at 7 days after SCI. Conclusion: Ginsenoside Rb1 (gRb1), with putative anti-apoptotic, angiogenic and neurotrophic actions, is a candidate agent for the treatment of patients with acute SCI.

Anti-oxidative nutrient rich diet protects against acute ischemic brain damage in rats

We evaluated the neuroprotective effects of an anti-oxidative nutrient rich enteral diet (AO diet) that contained rich polyphenols (catechins and proanthocyanidins) and many other anti-oxidative ingredients. Wistar rats were treated with either vehicle, normal AO diet (containing 100kcal/100mL, catechin 38.75mg/100mL and proanthocyanidin 19mg/100mL, 1mL/day), or high AO diet (containing 10 times the polyphenols of the normal AO diet) for 14 days, and were subjected to 90min of transient middle cerebral artery occlusion. The AO diet improved motor function, reduced cerebral infarction volume, and decreased both peroxidative markers such as 4-hydroxynonenal, advanced glycation end products, 8-hydroxy-2-deoxyguanosine and inflammatory markers such as monocyte chemotactic protein-1, ionized calcium-binding adapter molecule-1, and tumor necrosis factor-α. Our study has shown that an AO diet has neuroprotective effects through both anti-oxidative and anti-inflammatory mechanisms, indicating that nutritional control with polyphenols could be useful for patients with acute ischemic stroke.

Nerve protective effect of rhTPO and G-CSF on hypoxic ischemic brain damage in rats

ObjectiveTo observe the protection effect of rhTPO and granulocyte colony stimulating factor (G-CSF) on brain nerve after hypoxic ischemic brain damage (HIBD) in neonatal rats, exploring new ways for the laboratory basis of treatment for hypoxic ischemic encephalopathy, and provide for possible. MethodsA total of 120 newborn SD rats aging 7 d were randomly divided into control group, model group, TPO group and G-CSF group, using the method of blockingleft carotid artery to establish HIBD model. The left carotid artery was only seperated rather than blocked in the control group; after modeling, saline injection, rhTPO treatment and G-CSF treatment were adopted in the model group, TPO group and G-CSF group respectively. Then 10 rats of 4 groups were executed at Day 3, 7, 14 after modeling, brain tissue was extracted to observe the brain damage; Immunohistochemical method was used to observe the histopathological changes of brain tissue and changes of nest protein (nestin) expression. ResultsInjured brain mass of model group, TPO group and G-CSF group were significantly higher than that of control group at corresponding time point (P<0.05). Injured brain mass of TPO group and G-CSF group were significantly lower than that of model group (P<0.05), and with the increase of age, more significant increasing trend. At Day 3 after modeling, the expression of nestin positive cells in cerebral cortex of model group, TPO group and G-CSF group increased significantly than that of control group (P<0.05); nestin positive cells of G-CSF group outnumbered TPO group significantly (P<0.05). ConclusionsThe early TPO, G-CSF treatment of HIBD rats can improve brain function after hypoxia ischemia by neural protection. G-CSF can promote the differentiation of neural cells proliferation, and reduce degeneration and necrosis of nerve cells.

Neuroprotection of up-regulated carbon monoxide by electrical acupuncture on perinatal hypoxic-ischemic brain damage in rats.

This study investigated the neuroprotection and potential mechanism of carbon monoxide (CO) against perinatal hypoxic-ischemic brain damage in rats by electrical acupuncture (EA). Animal behavior, morphological changes, cystathionine beta-synthase (CBS), hypoxia-inducible factor-1α (HIF-1α), and heme oxygenase-1 (HO-1) expression levels, and CO content in rat cortex cells were determined. Results demonstrated that EA treatment decreased the slope behavior and increased the overhang behavior of perinatal rats. The treatment also decreased the number of positive cells. The activator and inhibitor of CBS aggravated and remitted the hypoxic damage in cortex cells, respectively. EA treatment decreased CBS expression level and increased HO-1 and HIF-1α expression levels in perinatal rat cortex cells. Compared with the control groups, the CO content of cortex cells in the EA treatment group significantly increased (**p < 0.01). We hypothesized that EA treatment increases cortical CO content to protect against hypoxic damage via the hydrogen sulfide/CBS-CO/HO-1-HIF-1α system. This study provided a significant reference for EA therapy and cued a novel protective mechanism for cerebral palsy.

The selective estrogen receptor modulator, bazedoxifene, reduces ischemic brain damage in male rat

While the estrogen treatment of stroke is under debate, selective estrogen receptor modulators (SERMs) arise as a promising alternative. We hypothesize that bazedoxifene (acetate, BZA), a third generation SERM approved for the treatment of postmenopausal osteoporosis, reduces ischemic brain damage in a rat model of transient focal cerebral ischemia. For comparative purposes, the neuroprotective effect of 17β-estradiol (E2) has also been assessed. Male Wistar rats underwent 60min middle cerebral artery occlusion (intraluminal thread technique), and grouped according to treatment: vehicle-, E2- and BZA-treated rats. Optimal plasma concentrations of E2 (45.6±7.8pg/ml) and BZA (20.7±2.1ng/ml) were achieved 4h after onset of ischemia, and maintained until the end of the procedure (24h). Neurofunctional score and volume of the damaged brain regions were the main end points. At 24h after ischemia–reperfusion, neurofunctional examination of the animals did not show significant differences among the three experimental groups. By contrast, both E2- and BZA-treated groups showed significantly lower total infarct volumes, BZA acting mainly in the cortical region and E2 acting mainly at the subcortical level. Our results demonstrate that: (1) E2 at physiological plasma levels in female rats is neuroprotective in male rats when given at the acute stage of the ischemic challenge and (2) BZA at clinically relevant plasma levels mimics the neuroprotective action of E2 and could be, therefore, a candidate in stroke treatment.

Effects of Early and Late Ischemic Preconditioning of the Brain on the Severity of Hippocampal Neuron Injury and the Degree of Neurological Deficit in Rats

The aim of the present work was to investigate the neuroprotective effects of early and late ischemic preconditioning (IPreC) in the acute phase of ischemic brain damage in rats. Single 5-min ischemic episodes of early IPreC were found not to produce significant neuroprotective effects as compared with controls, while three 5-min episodes of early IPreC led to significant increases in neurological deficit and increases in the level of neuron injury in hippocampal field CA1. Conversely, late IPreC, consisting of a single 5-min episode 24 h before modeling test ischemia, produced a significant neuroprotective effect, with decreased neurological deficit and retention of hippocampal field CA1 neuron viability.

Administration of mesenchymal stem cells and ziprasidone enhanced amelioration of ischemic brain damage in rats.

Ziprasidone is a benzisothiazolyl piperazine derivative that was developed from the chemically related antipsychotic drug tiospirone, and it improves neurological functions of the ischemic brain and is effective in treatment of schizophrenia. Mesenchymal stem cells (MSCs) are considered as a leading candidate for neurological regenerative therapy because of their neural differentiation properties in damaged brain. We investigated whether the transplantation of neural progenitor cells (NPCs) derived from adipose mesenchymal stem cells combined with ziprasidone enhances neuroprotective effects in an animal model of focal cerebral ischemia. In combination therapy groups, significant reduction of infarct volume and improvement of neurological functions were observed at 3 days after middle cerebral artery occlusion (MCAO) compared with monotherapy. Co-administration of ziprasidone and NPCs enhanced the anti-apoptotic effect and reduced the number of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive apoptotic cells compared with the NPCs alone group at 7 days after MCAO. Ziprasidone or the combination of ziprasidone and NPCs induced the expression of endogenous neurotrophic factor gene brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and glial cell-derived neurotrophic factor (GDNF). The immunohistochemical investigation revealed that the ziprasidone and NPCs attenuated the increased intensity of microglial marker (Iba-1) in the infarcted cortical area. Moreover, the number of transplanted NPCs on day 7 with combination therapy was significantly higher than with NPCs alone. These effects might be responsible for improved functional behavior and increased survival of NPCs. Our finding indicates that combination therapy of ziprasidone and NPCs enhances neuroprotection against ischemic brain injury.

5-Lipoxygenase Inhibitor Zileuton Inhibits Neuronal Apoptosis Following Focal Cerebral Ischemia

Previous studies from our laboratory demonstrated that zileuton, a selective 5-lipoxygenase (5-LOX) inhibitor, attenuates ischemic brain damage in rats of focal cerebral ischemia. Enormous evidences showed that inflammatory reaction and neuronal apoptosis are the two important pathophysiological events in ischemia-induced brain damage. Our previous studies demonstrate that zileuton attenuates ischemic brain damage via inhibiting inflammatory reaction. The present study was performed to explore whether 5-LOX inhibitor zileuton attenuates neuronal apoptosis following focal cerebral ischemia and further investigate the potent mechanisms underlying its neuroprotection. Adult male Sprague-Dawley rats underwent permanent middle cerebral artery occlusion (MCAO) for 72 h, then received intragastric gavage with zileuton or vehicle as a bolus after the onset of MCAO. Neurological deficit scores, cerebral infarct volume, and neuronal damage were measured 72 h after MCAO. TUNEL staining was performed to measure the extent of neuronal apoptosis. Reverse transcription-polymerase chain reaction was performed to determine the expression of caspase-1 mRNA. Western blot was performed to determine the expression of procaspase-3 and cleaved caspase-3 in rat brain. Neurological deficit scores, infarct volume, and neuronal damage were significantly attenuated by administration of zileuton. MCAO caused the elevation of neuronal apoptosis, which was significantly inhibited by the administration of zileuton. MCAO caused the over-expression of caspase-1 and cleaved caspase-3, both of which were significantly inhibited by the administration of zileuton. Expression of procaspase-3 was reduced after MCAO, which was significantly up-regulated by administration of zileuton. Our studies suggested that 5-LOX inhibitor zileuton reduces MCAO-induced brain damage and neuronal apoptosis, which might be associated with the inhibition of caspase-1 and the regulation of caspase-3.

Neuroprotection of the leaf and stem of Vitis amurensis and their active compounds against ischemic brain damage in rats and excitotoxicity in cultured neurons

Vitis amurensis (Vitaceae) has been reported to have anti-oxidant and anti-inflammatory activities. The present study investigated a methanol extract from the leaf and stem of V. amurensis for neuroprotective effects on cerebral ischemic damage in rats and on excitotoxicity induced by glutamate in cultured rat cortical neurons. Transient focal cerebral ischemia was induced by 2 h middle cerebral artery occlusion followed by 24 h reperfusion (MCAO/reperfusion) in rats. Orally administered V. amurensis (25–100 mg/kg) reduced MCAO/reperfusion-induced infarct and edema formation, neurological deficits, and neuronal death. Depletion of glutathione (GSH) level and lipid peroxidation induced by MCAO/reperfusion was inhibited by administration of V. amurensis. The increase of phosphorylated mitogen-activated protein kinases (MAPKs), cyclooxygenase-2 (COX-2), and pro-apoptotic proteins and the decrease of anti-apoptotic protein in MCAO/reperfusion rats were significantly inhibited by treatment with V. amurensis. Exposure of cultured cortical neurons to 500 μM glutamate for 12 h induced neuronal cell death. V. amurensis (1–50 μg/ml) and (+)-ampelopsin A, γ-2-viniferin, and trans-ɛ-viniferin isolated from the leaf and stem of V. amurensis inhibited glutamate-induced neuronal death, the elevation of intracellular calcium ([Ca 2+] i), the generation of reactive oxygen species (ROS), and changes of apoptosis-related proteins in cultured cortical neurons, suggesting that the neuroprotective effect of V. amurensis may be partially attributed to these compounds. These results suggest that the neuroprotective effect of V. amurensis against focal cerebral ischemic injury might be due to its anti-apoptotic effect, resulting from anti-excitotoxic, anti-oxidative, and anti-inflammatory effects and that the leaf and stem of V. amurensis have possible therapeutic roles for preventing neurodegeneration in stroke.

Combination therapy with bone marrow stromal cells and FK506 enhanced amelioration of ischemic brain damage in rats

AimsTransplantation of bone marrow stromal cells (MSCs) has been shown to ameliorate ischemic brain injury in animals. In the present study, we investigated whether the transplantation of MSCs combined with FK506, a clinically used immunosuppressant, enhanced neuroprotective effects in rat experimental stroke. Main methodsMale Sprague–Dawley rats underwent transient 90min middle cerebral artery occlusion (MCAO). Two or 6h after ischemia onset, the rats were randomly assigned to receive intravenous administration of MSCs plus FK506, MSCs alone, FK506 alone, or vehicle. Infarct volume, and neurological and immunohistological assessments were performed to examine the effects of these therapies. Key findingsIn 2-hour post-ischemia treatment groups, significant improvement of infarct volume and neurological scores were observed 1day after combination therapy compared with monotherapy, and this neuroprotection continued for 7days. Combination therapy significantly reduced the number of TUNEL-positive apoptotic cells, increased Bcl-2 expression, decreased Bax expression, and suppressed neutrophil infiltration and microglia/macrophage activation compared to monotherapy. In 6-hour post-ischemia treatment groups, a significant reduction of infarct volume, edema index, and neurological score was observed only in the combination therapy group. Moreover, the number of engrafted MSCs on day 7 with combination therapy was significantly higher than with MSCs alone. SignificanceCombination therapy using FK506 enhanced the anti-apoptotic and anti-inflammatory effects of MSCs and increased the survival of transplanted cells, leading to expansion of the therapeutic time window for MSCs.

Low-Power 2-MHz Pulsed-Wave Transcranial Ultrasound Reduces Ischemic Brain Damage in Rats

It is largely unknown whether prolonged insonation with ultrasound impacts the ischemic brain tissue by itself. Our goal was to evaluate safety and the effect of high-frequency ultrasound on infarct volume in rats. Thirty-two Long-Evans rats with permanent middle cerebral and carotid artery occlusions received either 2-MHz ultrasound at two levels of insonation power (128 or 10mW) or no ultrasound (controls). We measured cerebral hemorrhage, indirect and direct infarct volume as well as edema volume at 24h. No cerebral hemorrhages were detected in all animals. Exposure to low-power (10mW) ultrasound resulted in a significantly decreased indirect infarct volume (p = 0.0039), direct infarct volume (p = 0.0031), and brain edema volume (p = 0.01) compared with controls. High-power (128mW) ultrasound had no significant effects. An additional experiment with India ink showed a greater intravascular penetration of dye into ischemic tissues exposed to low-power ultrasound. Insonation with high-frequency, low-power ultrasound reduces ischemic brain damage in rat. Its effect on edema reduction and possible promotion of microcirculation could be used to facilitate drug and nutrient delivery to ischemic areas.

Zileuton Reduces Inflammatory Reaction and Brain Damage Following Permanent Cerebral Ischemia in Rats

5-Lipoxygenase inhibitor zileuton has been demonstrated to attenuate ischemic brain damage in rats of permanent focal cerebral ischemia in previous work. To further investigate the mechanism underlying zileuton's neuroprotection, adult male Sprague-Dawley rats underwent permanent middle cerebral artery occlusion (MCAO), then received treatment with zileuton or vehicle after the onset of ischemia. Neurological deficit, cerebral infarction, and morphological characteristic were measured 6 and 24 h after MCAO. The enzymatic activity of myeloperoxidase (MPO) was assessed 6 and 24 h after MCAO and the lipid peroxidation levels were evaluated by malondialdehyde assay. Expression of nuclear factor-kappa B (NF-kappaB) p65 in rat brain was detected by immunohistochemistry and Western blot. Expression of inducible nitric oxide synthase (iNOS) in rat brain was determined by RT-PCR and Western blot. Nitric oxide production in rat brain was also measured 24 h after MCAO. The concentration of TNF-alpha and IL-1beta in serum were detected by ELISA. Zileuton significantly reduced neurological deficit scores, cerebral infarct volume, MPO activity, and the lipid peroxidation levels. It also inhibited the expression of NF-kappaB and decreased the expression and activity of iNOS in rat brain. In addition, zileuton attenuated the release of TNF-alpha and IL-1beta in serum. Our results suggest that zileuton reduces inflammatory reaction and brain damage in a rat model of permanent focal cerebral ischemia. The neuroprotective effect of zileuton in cerebral ischemia might be associated with the inhibition of inflammatory reaction.

5-lipoxygenase inhibitor zileuton attenuates ischemic brain damage: involvement of matrix metalloproteinase 9

Objectives: Cerebral ischemia causes an increased expression and activation of 5-lipoxygenase (5-LOX) and matrix metalloproteinase 9 (MMP-9). Recent works demonstrated that the selective 5-LOX inhibitor zileuton down-regulates MMP-9 expression in vascular diseases and cancer. In the present work, we first studied the neuroprotective effect of zileuton on focal cerebral ischemia in rats and further investigated the effect of zileuton on the expression of 5-LOX and MMP-9 in ischemic brain.Methods: Adult Sprague–Dawley rats underwent permanent middle cerebral artery occlusion (pMCAO). The rats then received treatment with zileuton 5, 10 or 50 mg/kg or vehicle. Cerebral water content and infarct volume were measured 24 hours after pMCAO. Expression of 5-LOX messenger RNA (mRNA) and MMP-9 mRNA were determined by reverse transcription polymerase chain reaction. The levels of the proform and the active form of MMP-9 were detected by gelatin zymography.Results: Oral treatment of zileuton at 10 or 50 mg/kg significantly reduced cerebral water content and infarct volume. It also down-regulated the expression of 5-LOX mRNA and MMP-9 mRNA. Zileuton at 50 mg/kg could inhibit the active form of MMP-9.Conclusion: These results suggest that selective 5-LOX inhibitor zileuton attenuates ischemic brain damage in rats, which may be partly associated with MMP-9 inhibition.

Transplantation of a ventral mesencephalon-derived cell line, RTC4, reduces ischemic brain damage in rats

Transplantation of a ventral mesencephalon-derived cell line, RTC4, reduces ischemic brain damage in rats

Protection against ischemic brain damage in rats by immunophilin ligand GPI-1046

Protection against ischemic brain damage in rats by immunophilin ligand GPI-1046