Progesterone-Mediated Neuroprotection In Rats After Focal Cerebral Ischemia Reperfusion

BackgroundIschemic cerebrovascular disease (ICVD) with high incidence and high mortality andhigh morbidity, is a serious hazard to human health. Transient cerebral ischemia inducesselective, delayed neuronal death in the hippocampal CA1and delayed neurologicalfunctions. Neurological functions impairment, including deficiencies in learning andmemory performance, is common after ischemic stroke and burdens to the society andfamilies. Postmenopausal women are in an progesterone-deprived state and are at riskfor stroke and postmenopausal progesterone therapy reduces the risk. Investigations todate have demonstrated that progesterone are neuroprotective in animal models ofischemia.Progesterone is a steroid hormone secreted by the ovaries and adrenal glands.Neuroprotective mechanisms of progesterone include the classic receptor dependentmechanism and receptor-independent mechanism.Progesterone therapy improves neurological functions, including memory and learningprocesses in a global ischemia model. However, in our clinical practice, the incidence offocal cerebral ischemia is larger than global ischemia. Because of the differencesbetween ischemic modes, the paths of neuronal apoptosis, neurological damage andneurological functions are far away in focal and global ischemia. However, investigations to date have demonstrated that the underlying etiology, causes and burdenof stroke may be different, the effects of progesterone on neurological functions instroke are not well documented.ObjectiveIn our present study, to test the hypothesis that progesterone treatment woulddifferentially accelerate neurological functions recovery after focal brain ischemia, wehave extensively assessed the effects of progesterone treatment on focal cerebralischemia, and then evaluated the neurological function assessment, the proportion ofinfarction size, the expression of PKCβⅡ, NF-κB p65and IP3content after focalcerebral ischemia.Methods1. Cerebral ischemia model Using the modified middle cerebral artery occlusion(MCAO) model, animals were treated with transient MCAO (tMCAO) for2hours.2. Neurological function assessment Zeal Longa rating method was employed toassess the neurological functions.3. Determination of Proportion of infarction size The proportion of infarction sizewas evaluated by Image-Pro plus after stained by2,3,5-triphenyltetrazoliumchloride (TTC).4. Immunohistochemistry (IHC) We use IHC to detect the expression ofPKCβⅡand NF-κB p65.5. ELISA ELISA was used to analyze the IP3content in region around infarctionarea．6. Statistics Statistical analysis was performed using SPSS Statistics13.0software(SPSS Inc, Chicago, USA). All data are presented as means±SEM. Two-wayanalysis of variance, one-way ANOVA and post-hoc comparisons were made where appropriate. All differences were considered significant at p<0.05.ResultsOur data suggest that progesterone treatment reduced infarct size after tMCAO in adultSD rats. Progesterone recovery neurological functions against cerebralischemia-reperfusion injury on rats. The IP3content of DMSO group were all lowerthan that in the sham operation group and normal control group significantly(P<0．05)，and the IP3content of PROG treament group was higher than that in the DMSO groupsignificantly. Ischemia increases PKCβⅡ and NF-κB p65expression in the cortexwhile progesterone treatment decreases PKCβⅡ and NF-κB p65. These resultsindicated that progesterone may produce neuroprotective effects by restore thePKCβⅡ、NF-κB p65and IP3content in region around infarction area to rats.