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@#Objective To investigate the effects of recombinant tissue-type plasminogen activator (rt-PA) combined with mild hypothermia on the hemorrhagic transformation after cerebral ischemia-reperfusion within or out of the therapeutic time window in rats.Methods The focal cerebral ischemia-reperfusion 3 and 4 hours models of rats were established by middle cerebral artery occlusion (MCAO) 3 or 4 hours. The rats were randomly divided into the normal saline group (group NS), normothermia rt-PA group (group rt-PA), rt-PA combined with hypothermia group (group rt-PA +HT), and sham-operation group. Brain mild hypothermia was achieved after ischemia reperfusion and maintained 3 hours. Rats were sacrificed 24 h after ischemia reperfusion, and the amount of bleeding was measured.Results The amount of bleeding significantly reduced in the group rt-PA+HT compared with group rt-PA, which obviously increased in the group rt-PA compared with group NS ( P<0.05); there was a significant difference between rt-PA groups MCAO 3 hours and 4 hours ( P<0.05).Conclusion rt-PA can increase hemorrhagic transformation volume; hemorrhagic transformation volume is higher if treated by rt-PA within 3 h therapeutic time window than treated beyond the time window; mild hypothermia should possibly prevent the development of hemorrhagic transformation and prolong the therapeutic time window of thrombolytic intervention in ischemic stroke.
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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.