Total saponins of Panax Notoginseng modulate the expression of caspases and attenuate apoptosis in rats following focal cerebral ischemia-reperfusion

Ethnopharmacological relevance

Total saponins of Panax notoginseng (TSPN), main constituents extracted from Panax Notoginseng, a highly valued traditional Chinese medicine, have been shown to be an effective agent on cerebral infarction.

Aim of the study

The effects of TSPN on apoptosis and expressions of caspase-1, caspase-3 and caspase-8 were studied after cerebral ischemia for 2 h followed by reperfusion for 46 h in rats.

Materials and methods

Rats were subjected to transient middle cerebral artery occlusion (MCAO) model using the intraluminal thread. TSPN was administered intraperitoneally at 5 min before and 12 h, 24 h and 36 h after MCAO, respectively.

Results

TSPN (at the dose of 25 mg/kg) significantly attenuated TUNEL-positive cells and reduced the expression of caspase-1 and caspase-3 compared to the model group, while it had no obvious effect on the expression of caspase-8.

Conclusions

The neuroprotective effect of TSPN on focal ischemia may be related to inhibition of apoptosis and caspases activation.     

An-Gong-Niu-Huang Wan protects against cerebral ischemia induced apoptosis in rats: Up-regulation of Bcl-2 and down-regulation of Bax and caspase-3

Ethnopharmacological relevance

The An-Gong-Niu-Huang Wan (AGNH), a Chinese traditional medicine, has been used for treatment of cerebral diseases for centuries in China and other Asian countries, and is approved by the State Food and Drug Administration of China for the treatment of stroke. The aim of present study is to test the neuroprotective effects of AGNH on cerebral ischemia in rats and to explore the underlying mechanisms.

Materials and methods

75 Male Sprague-Dawley rats were randomly divided into 5 groups: sham, ischemia–reperfusion (I/R), and I/R plus 0.065 g/kg/d AGNH, 0.125 g/kg/d AGNH and 0.25 g/kg/d AGNH. Cerebral ischemia was induced by 1.5 h of middle cerebral artery occlusion (MCAO). Neurological functional deficits were evaluated according to Zea longa?s score, cerebral infarct area was measured by tetrazolium staining. Cell injury and apoptosis were assessed by Nissl staining and DNA fragmentation assay. The expression of Bax, Bcl-2 and caspase-3 were analyzed by Western blot.

Results

Rats subjected to MCAO exhibited worsened neurological score, infarct area, cell damage and apoptosis. These were all attenuated by AGNH (0.125 and 0.25 g/kg/d). Moreover, AGNH reversed cerebral ischemia induced decreases in Bcl-2 expression and increases in Bax and caspase-3 expression.

Conclusions

These results suggest that AGNH exerts neuroprotective effects, and the neuroprotection is likely to relate to depressed Bax/Bcl-2 ratio and caspase-3 level, leading to inhibition of apoptotic cell death.     

Neuroprotective effect of Momordica charantia in global cerebral ischemia and reperfusion induced neuronal damage in diabetic mice

Ethnopharmacological relevance

Momordica charantia L. (Cucurbitaceae) fruits have been used traditionally for centuries, especially for treating diabetes and associated complications.

Aim of the study

The present study was performed to evaluate neuroprotective effect of lyophilized M. charantia fruit juice against global cerebral ischemia and reperfusion induced neuronal injury in diabetic mice.

Materials and methods

Global cerebral ischemia induced by occluding both common carotid arteries for 10 min followed by 24 h reperfusion was used to induce neuronal injury. Ischemia-reperfusion induced neuronal injury was evaluated in terms of cerebral infarct size, generation of free radicals measured as thiobarbaturic acid reactive substances (TBARS), and neurological functions measured as short term memory and motor activity.

Results

The cerebral oxidative stress and damage, and neurological deficits were dose dependently attenuated by pre-treatment with the lyophilized M. charantia juice (200-800 mg/kg, p.o., o.d.). Moreover, M. charantia also exhibited dose dependent antihyperglycemic activity in diabetic mice.

Conclusions

These results suggest that M. charantia has potent neuroprotective activity against global cerebral ischemia-reperfusion induced neuronal injury and consequent neurological deficits in diabetic mice.     

Neuroprotective activity of Matricaria recutita Linn against global model of ischemia in rats

Ethnopharmacological relevance

Traditionally, the whole plant is used for various diseases, including neuronal disorders.

Aim of the study

To evaluate the neuroprotective effect of Matricaria recutita L. against global cerebral ischemia/reperfusion (I/R) injury-induced oxidative stress in rats.

Materials and methods

Neuroprotective activity was carried out by global cerebral ischemia on Sprague–Dawley rats by bilateral carotid artery (BCA) occlusion for 30 min followed by 60 min reperfusion. The antioxidant enzymatic and non-enzymatic levels were estimated along with cerebral infarction area and histopathological studies.

Results

The Matricaria recutita L. methanolic extract showed dose-dependent neuroprotective activity by significant decrease in lipid peroxidation (LPO) and increase in the superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and total thiol levels in extract treated groups as compared to ischemia/reperfusion group. Cerebral infarction area was significantly reduced in extract treated groups as compared to ischemia/reperfusion group.

Conclusion

The methanolic extract of Matricaria recutita L. showed potent neuroprotective activity against global cerebral ischemia/reperfusion injury-induced oxidative stress in rats.     

Protective effect of Ilex latifolia, a major component of "kudingcha", against transient focal ischemia-induced neuronal damage in rats

Aims of the study

Ilex latifolia (Aquifoliaceae), a primary component of “kudingcha”, has been used in Chinese folk medicine to treat various kinds of diseases including headaches, inflammatory diseases, and cardiac ischemic injury. The present study investigated the protective effect of the ethanol extract of Ilex latifolia against transient, focal, ischemia-induced neuronal damage.

Materials and methods

Transient focal ischemia was induced by 2 h middle cerebral artery occlusion followed by 24 h reperfusion (MCAO/reperfusion) in rats. After MCAO/reperfusion, brain infarction and neuronal death were measured by triphenyltetrazolium chloride and hematoxylin and eosin staining, respectively. Glutathione concentration and lipid peroxidation rate were measured. The expression levels of phosphorylated mitogen activated proteins kinases (MAPKs), cyclooxygenase 2 (COX-2), and anti-apoptotic and pro-apoptotic proteins were detected by Western blot.

Results

Ilex latifolia (50-200 mg/kg) significantly reduced MCAO/reperfusion-induced infarction and edema formation, neurological deficits, and brain cell death. Depletion of glutathione level and lipid peroxidation induced by MCAO/reperfusion were inhibited by administration of Ilex latifolia. The increase of phosphorylated MAPKs, COX-2, and proapoptotic proteins and the decrease of antiapoptotic protein in MCAO/reperfusion rats were significantly inhibited by treatment with Ilex latifolia.

Conclusion

Ilex latifolia ameliorated ischemic injury induced by MCAO/reperfusion in rats, and this neuroprotective effect might be associated with its anti-apoptotic effect, resulting from anti-oxidative and anti-inflammatory actions.     

Neuroprotective effect of Buyang Huanwu decoction against focal cerebral ischemia/reperfusion injury in rats--time window and mechanism

Ethnopharmacological relevance

Buyang Huanwu Decoction, a traditional Chinese medicine, consists of different herbal medicines, and has been traditionally used for centuries to treat paralysis and stroke. However, its optimal therapeutic time window and the mechanism are still unclear.

Aim of the study

This study was designed to explore the therapeutic time window and mechanism of Buyang Huanwu Decoction on transient focal cerebral ischemia/reperfusion injury.

Materials and methods

Middle cerebral artery occlusion was conducted in male Sprague-Dawley rats, and 40 g/kg of Buyang Huanwu Decoction was intragastrically infused at different time points, and the same dose was infused every 24 h for 3 days. The level of glutamate in cerebrospinal fluid and the expression of metabotropic glutamate receptor-1 RNA in striatum were detected before, during, and after ischemia/reperfusion. Neurological deficit scores and brain infarction volumes were measured at 72 h after reperfusion.

Result

Cerebral ischemia/reperfusion resulted in significant neurological deficit and extensive cerebral infarct volume, associated with a large amount of glutamate in cerebrospinal fluid and elevation of metabotropic glutamate receptor-1 RNA expression. Buyang Huanwu Decoction significantly suppressed the release of glutamate, and reduced the expression of metabotropic glutamate receptor-1 RNA. The neurological defect score and infarction volume were significantly improved by administration of Buyang Huanwu Decoction, when compared with the Ischemia group.

Conclusions

Administration of Buyang Huanwu Decoction, within 4 h of post-transient focal stroke, reduced significant cerebral ischemia/reperfusion damage. The neuroprotective mechanism of Buyang Huanwu Decoction is, in part, associated with the down-regulation of metabotropic glutamate receptor-1 RNA and inhibition of glutamate release resulting from cerebral ischemia.     

Neuroprotective effect of calycosin on cerebral ischemia and reperfusion injury in rats

Ethnopharmacological relevance

Radix Astragali has been commonly used as traditional herbal medicine in China for reinforcing vital energy, strengthening superficial resistance and promoting the discharge of pus and the growth of new tissue.

Aim of the study

The present study was to investigate the neuroprotective effect of calycosin isolated from the roots of Radix Astragali on cerebral ischemic/reperfusion injury.

Materials and methods

After 24 h of reperfusion following ischemia for 2 h induced by middle cerebral artery occlusion (MCAO), Sprague-Dawley rats were intragastrically administered different doses of calycosin (7.5, 15, 30 mg/kg, respectively). Neurological deficit, infarct volume, histopathology changes and some oxidative stress markers were evaluated after 24 h of reperfusion.

Results

Treatment with calycosin significantly ameliorated neurologic deficit and infarct volume after cerebral ischemia reperfusion. Calycosin also reduced the content of malondialdehyde (MDA), protein carbonyl and reactive oxygen species (ROS), and up-regulated the activities of superoxide dismutase (SOD), catalase and glutathione peroxidase (GSH-Px) in a dose-dependent manner. Moreover, calycosin can also inhibit the expression of 4-Hydroxy-2-nonenal (4-HNE).

Conclusion

These results suggest that calycosin has a neuroprotective effect against cerebral ischemia/reperfusion injury. The mechanism might be attributed to its antioxidant effects.     

Neuroprotective effects of Eleutherococcus senticosus bark on transient global cerebral ischemia in rats

Ethnopharmacological relevance

Eleutherococcus senticosus Maxim., classified into the family of Araliaceae, is used in a variety of diseases in traditional Korean medicine including ischemic heart disease.

Aim of the study

To determine the neuroprotective effects of Eleutherococcus senticosus on global cerebral ischemia.

Materials and methods

A four-vessel occlusion (4-VO) rat model was used to evaluate the potential protective effects against transient global cerebral ischemia ethanol extracts of Eleutherococcus senticosus was orally administered at doses of 3, 30, and 300 mg/kg twice at times of 0 and 90 min after reperfusion. The effects on memory deficit were investigated by using a Y-maze neurobehavioral test after brain ischemia, and the effects on hippocampal neuronal damage were measured 7 days after ischemia. The expressions of glial fibrillary acid protein (GFAP), CD11b antibody (OX-42), and cyclooxygenase-2 (COX-2) were investigated by immunohistochemistry.

Results

Oral administration of Eleutherococcus seticosus at 30, 100 and 300 mg/kg significantly reduced hippocampal CA1 neuronal death by 3.5%, 25.9% and 53.1%, respectively, compared with a vehicle-treated group. Oral administration of Eleutherococcus senticosus at 300 mg/kg inhibited 81.9% of the decrease in spontaneous alternation induced by 4-VOin the Y-maze test, and also attenuated ischemia-induced activation of COX-2, GFAP and OX-42 in the hippocampal CA1 region.

Conclusion

Eleutherococcus senticosus protects delayed neuronal death in the CA1 region of the hippocampus against global cerebral ischemia in rats with the recovery of spatial memory, which can be considered as the normal functioning of the hippocampus. Regarding the immunohistochemical study, the effect of Eleutherococcus senticosus may be attributable to its anti-inflammatory properties through the inhibition of COX-2 expression, microglia and astrocyte expression.     

Cerebralcare Granule,a Chinese herb compound preparation,improves cerebral microcirculatory disorder and hippocampal CA1 neuron injury in gerbils after ischemia–reperfusion

Aim of the study

Cerebralcare Granule^® (CG) is a Chinese herb compound preparation that has been used for treatment of cerebrovascular related diseases. However, the effect of post-treatment with CG on ischemia and reperfusion (I/R) induced cerebral injury is so far unclear.

Materials and methods

In present study, cerebral global I/R was induced in Mongolian gerbils by clamping bilateral carotid arteries for 30 min followed by reperfusion for 5 days, and CG (0.4 g/kg or 0.8 g/kg) was administrated 3 h after the initiation of reperfusion.

Results

Post-treatment with CG for 5 days attenuated the I/R-induced production of hydrogen peroxide in, leukocyte adhesion to, and albumin leakage from cerebral microvessels, and, meanwhile, protected neuron from death, reduced the number of caspase-3- and Bax-positive cells, and increased Bcl-2-positive cells in hippocampal CA1 region.

Conclusion

The results suggest that CG given after initiation of reperfusion is able to ameliorate cerebral microvascular dysfunction and hippocampal CA1 neuron damage caused by I/R.     

Ginseng total saponins enhance neurogenesis after focal cerebral ischemia

Ethnopharmacological relevance

Ginseng, the root of Panax ginseng C.A. Meyer, is one of the most commonly used healing herbs for stroke and chronic debilitating conditions in China. Ginsenosides are the main active principles for ginseng's efficacy, but the mechanisms have not been fully clarified.

Aim of the study

To test the hypothesis whether or not the administration of Ginseng total saponins (GTS) can enhance neurogenesis after focal cerebral ischemia, and thereby improve neurological deficits.

Materials and methods

Male Wistar rats received intraperitoneal injections of GTS dissolved at a dose of 25 mg kg⁻¹ d⁻¹ or normal saline (NS) of same volume 3 days before the permanent middle cerebral artery occlusion (MCAO) model establishment until the animals were killed at the time points of 1 d, 3 d, 7 d and 14 d. The neurological function was assessed blindly. BrdU immunostaining and double staining were performed by following the 3-steps method.

Results

(A) GTS-treated rats have better neurological scores compared with those in NS group at 14 d time point (p < 0.05); (B) the number of BrdU⁺ cells and BrdU⁺/NeuN⁺ cells in GTS group were significantly higher than those in NS group in the ipsilateral subventricular zone and in the ipsilateral infarct area after MCAO, respectively (p < 0.05 or p < 0.01); (C) the increase of the number of BrdU⁺/NeuN⁺ cells highly correlated with the decrease of neurological scores. Coefficient correlation r = −0.828 (p < 0.01).

Conclusion

GTS can improve neurological deficits after focal cerebral ischemia by inducing endogenous neural stem cells activation and thereby enhance adult central nervous system regeneration.     

Effect of ginkgolide B on striatal extracellular amino acids in middle cerebral artery occluded rats

Ethnopharmacological relevance

Ginkgo biloba leaves are traditionally used in China for its health-promoting properties. There is substantial experimental evidence to support the view that Ginkgo biloba extracts have neuroprotective properties under conditions such as hypoxia/ischemia.Although a number of studies have investigated that ginkgolide B, a purified terpene lactone component extracted from Ginkgo biloba leaves, is available “platelet activating factor (PAF) receptors antagonist”, “antioxidant” with a variety of actions, very little has been performed to explore the effect of ginkgolide B on extracellular amino acids in experimental animal of focal cerebral ischemia/reperfusion. In this study, the effect of ginkgolide B on the striatal extracellular levels of glutamate (Glu), aspartic acid (Asp), glycine (Gly) and γ-aminobutyric acid (GABA) was evaluated in rats undergone middle cerebral artery occlusion (MCAO) for 1 h followed by 23 h reperfusion.

Materials and methods

The Sprague-Dawley (SD) rats received intraperitoneal injections of ginkgolide B dissolved at a dose of 10 mg kg⁻¹ d⁻¹, 20 mg kg⁻¹ d⁻¹, or normal saline (NS) of same volume 3 d before the middle cerebral artery occlusion model establishment. Extracellular concentrations of glutamate, aspartic acid, glycine and GABA in striatum were monitored using in vivo microdialysis and analyzed using high-performance liquid chromatography. Excitotoxic index (EI) was calculated. Twenty-four hours after MCAO, the cerebral infarct volume was detected on 2,3,5-triphenyltetrazolium chloride-stained coronal sections.

Results

The result showed that administration of ginkgolide B (10 or 20 mg kg⁻¹) before ischemia reduced the ischemia-induced elevation of levels of glutamate, aspartic acid and glycine, increased the elevation of extracellular GABA, decreased the excitotoxic index and diminished the volume of cerebral infarction, although a clear concentration-response relationship was not found.

Conclusions

The present work provides the first evidence that ginkgolide B protects against cerebral ischemic injury by inhibiting excitotoxicity by modulating the imbalance of excitatory amino acids versus inhibitory amino acids, which may support the traditional use of Ginkgo biloba leaves for the treatment of stroke.     

Role of Ocimum basilicum L. in prevention of ischemia and reperfusion-induced cerebral damage, and motor dysfunctions in mice brain

Ethnopharmacological relevance

The genus Ocimum (Lamiaceae) has a long history of use as culinary and medicinal herbs. Many species are used for their antioxidant and neuroprotective activity in various parts of the world. Ocimum basilicum Linn. has been used traditionally for the treatment of anxiety, diabetes, cardiovascular diseases, headaches, nerve pain, as anticonvulsant and anti-inflammatory, and used in a variety of neurodegenerative disorders.

Aim of the study

The present study is designed to investigate the effect of ethyl acetate extract of Ocimum basilicum leaves on ischemia and reperfusion-induced cerebral damage, and motor dysfunctions in mice.

Materials and methods

Global cerebral ischemia was induced by bilateral carotid artery occlusion for 15 min followed by reperfusion for 24 h. Cerebral infarct size was measured using triphenyltetrazolium chloride staining. The concentration of thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH) content was determined by colorimetric assay. Short-term memory was evaluated using elevated plus-maze. Inclined beam walking was employed to assess motor coordination. Bilateral carotid artery occlusion followed by reperfusion produced significant increase in cerebral infarct size and lipid peroxidation (TBARS), and reduced GSH content, and impaired short-term memory and motor coordination.

Results

Pre-treatment with standardized ethyl acetate extract of Ocimum basilicum (100 and 200 mg/kg, p.o.) markedly reduced cerebral infarct size and lipid peroxidation, restored GSH content, and attenuated impairment in short-term memory and motor coordination.

Conclusion

The results of the study suggest that Ocimum basilicum could be useful clinically in the prevention of stroke.     

三生饮对脑缺血大鼠大脑皮质区caspase-3表达的影响

目的探讨三生饮对局灶性脑缺血大鼠大脑皮质区caspase-3蛋白表达的影响。方技建立大鼠局灶性脑缺血再灌注模型，采用SABC免疫组织化学方法，检测再灌注后6h、12h、24h大鼠大脑皮质区的caspam-3阳性细胞数，比较模型组与三生饮组的差别。结果与模型组相比，三生饮组各时间点的caspase-3阳性细胞数明显较低（P〈0．05）。结论三生饮可能通过抑制caspase-3阳性细胞的表达，而对脑缺血再灌注损伤起到保护作用。     

Xiao-Xu-Ming decoction preserves mitochondrial integrity and reduces apoptosis after focal cerebral ischemia and reperfusion via the mitochondrial p53 pathway

Ethnopharmacological relevance

Xiao-Xu-Ming decoction (XXMD) has been used to treat stroke and other neurological diseases for more than 1000 years. The purpose of this study was to investigate the effects of XXMD on mitochondrial damage and apoptosis after cerebral ischemia and reperfusion.

Materials and methods

Male Sprague-Dawley rats were randomly divided into 3 groups: sham, cerebral ischemia and reperfusion (I/R), and cerebral ischemia and reperfusion plus XXMD (60 g/kg/day) (XXMD60). Focal cerebral ischemia and reperfusion models were induced by middle cerebral artery occlusion. Cerebral ischemic injury was evaluated by hematoxylin and eosin staining. Ultrastructural features of mitochondria in the penumbra of the ischemic cortex were analyzed by transmission electron microscopy. Apoptosis was evaluated by terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphosphate nick end labeling (TUNEL) staining and cleaved caspase 3 immunohistochemistry. Proteins in the mitochondrial p53 pathway were detected by western blot and immunofluorescence.

Results

The results showed that XXMD treatment markedly attenuated ischemic changes, preserved mitochondrial integrity, and significantly reduced apoptosis. In addition, we found that XXMD treatment reduced p53 and Bax levels and increased Bcl-2 levels in mitochondrial fractions. XXMD significantly blocked the release of cytochrome c and Smac/Diablo from mitochondria, and inhibited activation of caspase 9 and caspase 3 in cytoplasmic fractions. Increased expression of c-IAP1 was observed in the XXMD60 group.

Conclusions

The findings demonstrated that XXMD protected mitochondria from ischemic injury and inhibited apoptosis. The mitochondrial p53 pathway could be partially involved in the protective effects.     

Effects of Scutellaria baicalensis on chronic cerebral hypoperfusion-induced memory impairments and chronic lipopolysaccharide infusion-induced memory impairments

Ethnopharmacological relevance

Extracts of the roots of Scutellaria baicalensis Georgi (Labiatae) have been widely used to relieve fever related to bacterial infection and inflammatory diseases in traditional Korean medicine and have been reported to be effective in brain diseases.These experiments were conducted to examine the effects of oral administration of Scutellaria baicalensis extracts on the rescue of memory impairments induced by chronic cerebral hypoperfusion or chronic lipopolysaccharide (LPS) infusion. In addition, the underlying mechanisms of these effects were investigated.

Materials and methods

In the first experiment, chronic cerebral hypoperfusion was induced in male Wister rats by bilateral common carotid artery occlusion (BCCAo). Daily administration of Scutellaria baicalensis extracts was started on 20 day after BCCAo and given for 40 days. A Morris water maze was then used to evaluate the status of the hippocampal-dependent spatial learning and hippocampal mitogen-activated protein kinase (MAPK) signaling was examined in control rats, rats with chronic cerebral hypoperfusion, and rats with chronic cerebral hypoperfusion that was administered Scutellaria baicalensis. In the second experiment, hippocampal microglial activation was induced by chronic infusions of LPS into the fourth ventricle of Fisher-344 rat brains. Daily administration of Scutellaria baicalensis extracts was started on 7 day after the surgery of LPS infusion and given for 32 days. Spatial memory and hippocampal microglial activation was then examined in control rats with an artificial cerebrospinal fluid infusion, rats with chronic LPS infusion, and rats with chronic LPS infusion that were administered Scutellaria baicalensis.

Results

Rats that received chronic cerebral hypoperfusion or chronic LPS infusion showed spatial memory impairments relative to their control rats; however, these symptoms were reduced by daily administration of Scutellaria baicalensis. Administration of Scutellaria baicalensis mitigated alterations of hippocampal MAPK signaling by chronic cerebral infusion and microglial activation by chronic LPS infusion.

Conclusions

These results indicate that Scutellaria baicalensis may possess therapeutic potential for the prevention of Alzheimer's disease and vascular dementia.     

Neuroprotective effects of Xiao-Xu-Ming decoction against ischemic neuronal injury in vivo and in vitro

Ethnopharmacological relevance

Xiao-Xu-Ming decoction (XXMD) has long been employed clinically to treat stroke in traditional Chinese Medicine.

Aim of the study

To investigate the neuroprotective effects of XXMD in vivo and in vitro stroke models and determine involved mechanisms.

Materials and methods

Two models (four-vessel occlusion in adult Wistar rats and oxygen–glucose deprivation primary cultured neurons) were employed to mimic ischemia-reperfusion damage, in vivo and in vitro, respectively. The effects of XXMD were investigated with respect to neuronal damage, activity of caspase-3 and expression of Bcl-2 in CA1 region of hippocampus after ischemia. The cognitive ability was measured 7 days after ischemia/reperfusion by using Morris water maze.

Results

Oral administration of XXMD significantly increased the density of neurons that survived in the CA1 region of hippocampus on the 3rd and 7th day after transient global ischemia was induced in a dose-dependent manner. XXMD ameliorated severe deficiencies in spatial cognitive performance induced by transient global ischemia. Inhibition of caspase-3 activity and up-regulation of Bcl-2 expression were induced in the high dose of XXMD-treated rats after ischemia. In oxygen–glucose deprivation model, both XXMD extract and drug-containing serum prepared from blood of high dose of XXMD-treated rats inhibited apoptotic neuronal death at 24 h after reoxygenation.

Conclusions

Our results clearly demonstrated that XXMD is neuroprotective and appears to influence deleterious pathological processes that are activated after the onset of ischemia.