ABSTRACT
Objective To study the hippocampal corticotropin releasing hormone (CRH) mRNA expression and neuroprotective mechanism of adrenocorticotropic hormore (ACTH) in immature rats after N-methyl-D-aspartate (NMDA)-induced spasm seizures.Methods Sixty 10-day-old Wistar rats were randomly divided into blank control group,NMDA-induced seizure group and ACTH treatment group (n=20).Rats in the blank control group did not give any treatment;rat models of infantile spasm in the NMDA-induced seizure group and ACTH treatment group were induced by intraperitoneal injection of NMDA (7 mg/kg) for a consecutive 7 d;3 h after NMDA injection,intraperitoneal injection of ACTH 0.5 mg/(kg· d) was performed in the rats of ACTH treatment group,and NMDA-induced seizure group was given an equal volume of saline.By in situ hybridization (ISH),the mean optical density of CRH mRNA-positive neurons in the hippocampus was measured.Results In the ACTH treatment group,the latencies of epileptic seizures one week after treatment were significantly prolonged as compared with those before treatment,and the scores of epileptic seizures one week after treatment were significantly decreased as compared with those before treatment (P＜0.05);the latencies of epileptic seizures were significantly prolonged and the scores of epileptic seizures were significantly decreased in the ACTH treatment group as compared with those in the NMDA-induced seizure group (P＜0.05).The CRH mRNA expression in NMDA-induced seizure group was significantly increased as compared with that in the blank control group (P＜0.05),and the CRH mRNA expression in the ACTH treatment group was significantly decreased as compared with that in the NMDA-induced seizure group (P＜0.05).Conclusion Systemic ACTH has neuroprotective effect via down-regulating the hippocampal CRH mRNA expression.
ABSTRACT
@#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.