Improvement of autophagy dysfunction as a potential mechanism for environmental enrichment to protect blood-brain barrier in rats with vascular cognitive impairment

•Environmental enrichment (EE) can attenuate cognitive decline in chronic cerebral hypoperfusion (CCH) rats.•EE can ameliorate blood-brain barrier (BBB) injury caused by CCH.•EE can improve the autophagy dysfunction, which may mediate the protective effect of EE on BBB. Vascular cognitive impairment (VCI) is the second most common cause of dementia after Alzheimer’s disease, and the cognitive impairment is one of the common effects of VCI. Unfortunately, it lacks effective therapeutic treatments at present. In our previous study, environmental enrichment (EE), as an early intervention for lifestyle modification, can ameliorate cognitive impairment by attenuating hippocampal blood-brain barrier (BBB) injury in chronic cerebral hypoperfusion (CCH) rats. However, the underlying mechanism remains unclear. Here, we found CCH rats in the standard environment (SE) developed cognitive impairment and BBB damage, which were significantly alleviated with the EE intervention. Meantime, EE improved the autophagy dysfunction caused by CCH in the hippocampus of rats, suggesting that the effect of EE on cognitive function and BBB may be related to the improvement of autophagy pathway.