Echinacoside Alleviates Cognitive Impairment in Cerebral Ischemia Rats through α7nAChR-Induced Autophagy

Objectives:To evaluate the effect of echinacoside(ECH)on cognitive dysfunction in post cerebral stroke model rats.Methods:The post stroke cognitive impairment rat model was created by occlusion of the transient middle cerebral artery(MCAO).The rats were randomly divided into 3 groups by a random number table:the sham group(sham operation),the MCAO group(received operation for focal cerebral ischemia),and the ECH group(received operation for focal cerebral ischemia and ECH50 mg/kg per day),with 6 rats in each group,The infarct volume and spatial learning were evaluated by triphenyl tetrazolium chloride staining and Morris water maze.The expression of α7 nAChR in the hippocampus was detected by immunohistochemistry.The contents of acetylcholine(ACh),malondialdehyde(MDA),glutathione(GSH),superoxide dismutase(SOD),activities of choline acetyltransferase(ChAT),acetylcholinesterase(AChE),and catalase(CAT)were evaluated by enzyme linked immunosorbent assay.The neural apoptosis and autophagy were determined by TUNEL staining and LC3 staining,respectively.Results:ECH significantly lessened the brain infarct volume and ameliorated neurological deficit in infarct volume and water content(both P<0.01).Compared with MCAO rats,administration of ECH revealed shorter escape latency and long retention time at 7,14 and 28 days(all P<0.01),increased the α7 nAChR protein expression,ACh content,and ChAT activity,and decreased AChE activity in MCAO rats(all P<0.01).ECH significantly decreased MDA content and increased the GSH content,SOD,and CAT activities compared with MCAO rats(all P<0.05).ECH suppressed neuronal apoptosis by reducing TUNEL-positive cells and also enhanced autophagy in MCAO rats(all P<0.01).Conclusion:ECH treatment helped improve cognitive impairment by attenuating neurological damage and enhancing autophagy in MCAO rats.