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@#Objective To investigate the effect of BPI-1095 on caspase-3 protein expression in middle artery occlusion(MCAO) rats.Methods Cerebral ischemia was induced with MCAO in adult male SD rats.Rats were randomly subjected into 6 groups with 15 rats in each group.Each rat has been given tested medication of different dosage and was sacrificed 24 h after treatment.The area of infarction was measured on each slice by image analysis system.Meanwhile,immunohistochemistry staining was used to identify caspase-3 expression in ischemic brain tissue.Results The infarcted area were significantly decreased in big and moderate dose treated rats(P<0.05,vs the placebo group).The expression of caspase-3 protein decreased in contralateral and ipsilateral hemisphere areas.The caspase-3 positive cell was significantly decreased in rats treated with big doses compared with placebo-or ASA-treated rats.Conclusion BPI-1095 shows neuroprotection in MCAO rats,which may related with the inhibition of caspase-3 expression resulting in apoptosis in penumbra.
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@#ObjectiveTo investigate the neuroprotective effects of different doses of BPI-1095 on infarct volume and neurological outcome in middle cerebral artery occlusion(MCAO) rats.MethodsCerebral ischemia model was induced with MCAO in adult male SD rats. 10 minutes after surgery, rats were randomly subjected into six groups with 15 rats in each group. Each rat has been given different dosage tested medication and was sacrificed 24 h after treatment. Neurological functional behaviour tests were performed 4 h and 24 h after treatment. After the final behaviour test, 7 or 8 rats (remain 5 rats for brain tissue stain) were randomly picked up from each group. Their infarction volume was measured with image analysis system after 2% triphenyl-tetrazolium chloride (TTC) stain. ResultsHigh dose (240 mg/kg) and moderate dose (80 mg/kg) of BPI-1095 were able to improve the neurological deficit in MCAO rats (P<0.05, vs vehicle-treated group), as well as they decrease the infracted volume (P<0.05, vs the vehicle-treated group ) 24 h after ischemia.Conclusion80～240 mg/kg BPI-1095 is able to improve neurological deficit effectively and reduce infarct volume significantly.
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@#ObjectiveTo observe the therapeutic benefit of administration of endothelial cells derived from rat bone marrow cells in ischemic stroke rats and to explore the related mechanism.MethodsPrepared endothelial cells from bone marrow stromal cells (BMSC) of rats, which were multiplied and differentiated in the medium with 400ng/ml rhGM-CSF in vivo. Rats were subjected to permanent cerebral middle artery occlusion (MCAO) models(n=45). Injected intravenously via tongue vein with 3×106 endothelial cells 24 h after stroke for test groups(n=15); injected same amount PBS for control group 1(n=15); control groups without any intervention after stroke (n=15). Neurologic functional behaviour tests (postural reflex test, limb use asymmetrical test and corner test) were performed before transplantation and 1,3,5,7,14 d after stroke. Meanwhile, immunohistochemistry staining was used to identify for vascular endothelial growth factor (VEGF) and its receptor FLK-1 expression in ischemic brain tissue.ResultsSignificant recovery of neurological function was detected in rats treated with endothelial cells on the 7th day and 14th day after stroke, compared with control group 1 and group 2(P<0.05);The number of positive cells of VEGF, FLK-1 were significant more in the peri-ischemic tissue and ipsilateral cortex, compared with non-ischemic hemisphere. The maximum number of positive cells was in the test group which was treated with endothelial cells(P<0.05);VEGF was mainly expressed at neurons, glial cells and part of endothelial cells; FLK-1 was mainly expressed at endothelial cells and part of neurons and glial cells;capillary hyperplasia was demonstrated more at the ischemic hemisphere in the rats treated with endothelial cells, compared with control group 1 or 2.ConclusionEndothelial cells derived from bone marrow cells in rats could improve neurological outcome in rats with ischemic stroke. The effect starts to be significant on the 7th day after transplantation and it shows more significant effect on the 14th day. Endothelial cells transplantation will enhance VEGF, FLK-1 expression at ischemic area and increases capillary hyperplasia formation, which may relate to the potential mechanism of neurological outcome improvement post stroke in rats.
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OBJECTIVE: Transplantation of stem cell, especially neural stem cell, has been proven effective in treating nervous system diseases in animal models,which provides new hopes for recovery of nerve functions in patients suffering from various nervous system diseases. Multiple studies have been conducted on the role of neural stem cells in repairing nerve functions, and several hypotheses have been proposed to explain how the stem cells or neural stem cells acts to recover nerve function.DATA SOURCES: We searched Medline for English articles from January 1997 to August 2003 with stem cell, neural stem cell, bone marrow stromal cell, stroke, ischemic injury, nervous system disease, and neurotrophic factor as the keywords. We also searched Wangfang database for Chinese articles with the same keywords from January 2003 to December 2004.STUDY SELECTION: The articles found in these two databases were primarily screened with the inclusion criteria as follow: the subjects should be animals or human; and the study should be the basic and/or clinical researches on(neural) stem cells.DATA EXTRACTION: Totally 72 English and Chinese articles were found in the two databases, among which 14 articles were closely associated with the present study and 10 were indirectly related. Eight articles were excluded for repetition in the contents. Finally 16 articles were included for analysis.DATA SYNTHESIS: The full text of the articles were reviewed and summarized. The results of these articles suggest that neural stem cells are valuable in treating cerebral vascular diseases, brain and spine injury, nerve degeneration diseases, and peripheral nerves diseases.CONCLUSION: Stem cells, especially neural stem cells, play active roles in treating nervous systeme diseases such as differentiation promotion, nerves nourishing, and nerve substitute.
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@#ObjectiveTo explore the feasibility of bone marrow stromal cells (BMSC) of rats differentiating into endothelial cells.MethodsBone marrow cells were obtained by an aseptic technique. Afterwards, the obtained cells were divided into two groups: cells in test group were propagated in 1640 medium with recombinant human GM-CSF (rhGM-CSF) (400ng/ml), and that in control group were propagated in medium with 1640 medium only. The differentiated cells were detected by specific immunology marker by immunocytochemistry and immunofluorescence at day 8.ResultsThe differentiated cells demonstrated the characters of endothelial cells under phase contrast microscopy. Cells of the test groups demonstrated specific characters by immunocytochemistry stain.ConclusionBone marrow stromal cells can multiply vigorously and differentiate into cells with endothelial cells characters in the medium with high concentration rhGM-CSF.