Rosuvastatin Improves Cerebral Hemodynamics And Ameliorates Cognitive Impairment In Rats With Chronic Cerebral Hypoperfusion

Background:Chronic cerebral hypoperfusion(CCH)is a common consequence of various cerebral vascular disorders,hemodynamics and blood composition changes,which can lead to neurodegenerative injury and cognitive dysfunction.Therefore,it is important to take measures to prevent or reverse its development.Previous studies have shown that rosuvastatin,a novel statins,whose pleiotropic effects is independent of lipid-lowering effect and it can stimulate angiogenesis and neuroprotection after acute ischemic stroke.However,its benefit for chronic cerebral hypoperfusion remains unknown.Objective:To investigate the effects of rosuvastatin on cerebral blood flow and cognitive function in rats with chronic cerebral hypoperfusion,and preliminaryly to explore its mechanisms.Methods:Eighty Sprague-Dawley rats were randomly divided into five groups:Sham group,Vehicle group(2-week group and 4-week group),Rosuvastatin-treated group(2-week group and 4-week group).Both vehicle and treated group rats were treated with bilateral common carotid artery occlusion(BCCAO).Then rats in the treated group were intravenously injection with rosuvastatin(0.2 mg/kg/day)daily for 14 days beginning 24 hours after BCCAO.The vehicle group was given the same amount of saline.The MRI 3D ASL technique was used to scan cerebral blood flow(CBF)at pre-occlusion,BCCAO,1,2,3,and 4 weeks after operation in vehicle and treated groups.Morris water maze test deteced spatial memory abilities of the treated and vehicle rats at 2 and 4 weeks after BCCAO.Immunofluorescence staining was used to detect the expression of CD34,GFAP,NeuN and Caspase-3 positive cells in hippocampus.Results:CBF decreased significantly after BCCAO in both rosuvastatin-treated and vehicle groups and then increased gradually.The CBF of the treated group was basically recovered to baseline levels at 1 or 2 weeks after BCCAO.But it took the vehicle group 4 weeks to restore to baseline.The vertebral artery(VA)diameter of the treated group was greater than that of the vehicle group(p<0.05),and the recovery of CBF and the dilation of VA were more evident during the administration period.Similarly,the escape latency of the treated group rats was also less than the vehicle group in Morris Water Maze test.In addition,the number of CD34~+and NeuN~+cells in the hippocampus of the treated group was more than that in the vehicle group(p<0.01),while the number of GFAP~+and Caspase-3~+cells was less than in the vehicle group(p<0.01).Conclusion:Rosuvastatin can accelerate the recovery of cerebral blood flow in CCH rats,which may be related to the dilation of VAs and angiogenesis;and its effects on reducing astrocyte activation and neuroprotection may help to ameliorate cognitive dysfunction in CCH rats.