Treadmill exercise improve cognitive function of cerebral ischemia-reperfusion rats by weakening endoplasmic reticulum stress-mediated apoptosis

Abstract

AbstractBackground:Recent evidence has suggested the neuroprotective effects of exercise preconditioning on cerebral ischemia-reperfusion injury (CI/R) rats. However, the mechanism is still unclear. So, the aim of the present study was to explore the possible mechanism of 4 weeks treadmill exercise preconditioning in improving cognitive function and impairment of neurological function in the cerebral ischemia reperfusion (CI/R) rats by measuring the blood-brain barrier(BBB), cerebral water content, neural cell apoptosis and the expressions of endoplasmic retieulum (ER) stress and apoptosis related protein in CI/R rats. 63 healthy adult male SD rats were randomly divided into sham group, cerebral ischemia-reperfusion group (CI/R group) and CI/R treated with exercise preconditioning group (CI/R+Ex group). Then rats in CI/R+Ex group were submitted to 4 weeks of incremental load treadmill exercise (5 days per week for 4 weeks). After exercise, rats of CI/R model group and CI/R exercise group underwent cerebral ischemia induction through occlusion of middle cerebral artery occlusion followed by reperfusion. Subsequently, the neurological deficits score was assessed at 24 h after CI/R and learning and memory abilities of rats were evaluated at 72 h after CI/R using water maze test in all group rats. Then the water content of rat brain tissue was measured by dry-wet method, BBB permeability based on the extravasation of evans blue. The ER-stress and apoptosis-related protein expression were detected by western blot.Results:Treadmill exercise preconditioning significantly prevented ischemia-induced memory dysfunction and impairment of neurological function, reduced brain edema and BBB leakage. Western blot showed that exercise preconditioning significantly reduced the expression of the ER-stress-related proteins PERK, EIf2a, ATF4, CHOP and the apoptotic protein caspase-12 expression.Conclusions:Our results suggest that the treadmill exercise preconditioning improves neurobehavioral deficits and cognitive function by inhibiting ER stress via the PERK/Eif2a/ATF4/CHOP pathway and ameliorating BBB disruption which reduces the brain edema.