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Amyloid-β(Aβ),responsible for cognitive impairment in Alzheimers disease(AD),has been shown to accumulate in ischemic brain.Autophagy plays an important role in the secretion and elimination of Aβ in AD.Previous studies have demonstrated that physical exercise(PE)is beneficial in ischemic brain recovery by mitigation of autophagy.PE can also alleviate post-stroke cognitive impairment(PSCI),but the underlying mechanism is still not clear.The present study aimed to determine the protective effect of PE on cognitive impairment after stroke and the role of autophagy and Aβ deposits in PSCI.Material and Methods:A total of 170 male stroke susceptible spontaneous hypertensive rats(SHR)were randomly divided into normal group(n=10),sham group(n=10),control group(n=40)after left transient middle cerebral artery occlusion(tMCAO),physical exercise group(n=30),saline injection group(n=40)and 3-methyladenine(3-MA)injection group(n=40).Rats of PE group start training in an electric running wheel at the third day after tMCAO.Intracerebroventricular injection of 3-MA mediated inhibition of autophagosome accumulation was performed at 24 hours after tMCAO to detect the effect of autophagy on Aβ deposits.Cognitive function was evaluated using the Morris water maze and novel object recognition(NOR)tests.Autophagy(LC3)and Aβ(Aβ1-16)expression as well as the role of associated proteins(APP,BACE1 and PS-1)were assessed by immunofluorescence staining and western blot analyses.PI3K/Akt/mTOR signaling pathway involved in the molecular regulation of autophagy.The protein expression of PI3K,p-PI3K,Akt,p-AKT,mTOR,and p-mTOR was observed by western blot analyses.Result: We found that new object recognition discrimination index decreased progressively with the time after surgery(P<0.01)and spatial learning memory observed by Morris water maze was also declined after tMCAO(P<0.05)in SHR.Besides,the accumulation of autophagosome and Aβ were evident in the peri-infarct region of SHR.Inhibition of autophagy by 3-MA contributed to reduce Aβ deposits and improve the new object recognition memory and spatial learning memory in SHR after tMCAO.Furthermore,physical exercise,which ameliorated cognitive impairment after stroke in SHR,also reduced the accumulation of autophagosome and Aβ.PE reduced the ratio of LC3Ⅱ/LC3Ⅰ(P<0.001)and the expression of APP(P<0.05),BACE1(P<0.01).Importantly,PI3K/Akt/mTOR signaling pathway was dramatically activated in the peri-infarct region of SHR after physical exercise training.Conclusion:Cerebral infarction causes cognitive impairment in SHR.Physical exercise inhibits autophagy and further reduces Aβ production to improve cognitive function in SHR after tMCAO,possibly associated with activating the PI3K/AKT/mTOR signaling pathway.