Enriched environment boosts the post-stroke recovery of neurological function by promoting autophagy

Autophagy is crucial for maintaining cellular homeostasis,and can be activated after ischemic stroke.It also participates in nerve injury and repair.The purpose of this study was to investigate whether an enriched environment has neuroprotective effects through affecting autophagy.A Sprague-Dawley rat model of transient ischemic stroke was prepared by occlusion of the middle cerebral artery followed by reperfusion.One week after surgery,these rats were raised in either a standard environment or an enriched environment for 4 successive weeks.The enriched environment increased Beclin-1 expression and the LC3-II/LC3-I ratio in the autophagy/lysosomal pathway in the penumbra of middle cerebral artery-occluded rats.Enriched environment-induced elevations in autophagic activity were mainly observed in neurons.Enriched environment treatment also promoted the fusion of autophagosomes with lysosomes,enhanced the lysosomal activities of lysosomal-associated membrane protein 1,cathepsin B,and cathepsin D,and reduced the expression of ubiquitin and p62.After 4 weeks of enriched environment treatment,neurological deficits and neuronal death caused by middle cerebral artery occlusion/reperfusion were significantly alleviated,and infarct volume was significantly reduced.These findings suggest that neuronal autophagy is likely the neuroprotective mechanism by which an enriched environment promotes recovery from ischemic stroke.This study was approved by the Animal Ethics Committee of the Kunming University of Science and Technology,China(approval No.5301002013855)on March 1,2019.