Enriched environment remodels the central immune environment and improves the prognosis of acute ischemic stroke in elderly mice with chronic ischemia

With the aging of many populations, cognitive and motor dysfunction caused by ischemic stroke (IS) secondary to long-term chronic cerebral ischemia presents a global problem. Enriched environment (EE), a classic paradigm of environment response and genetic interaction, has shown tremendous influence on the brain. This research aimed to investigate the potential effect of EE on cognitive and motor function in mice with chronic cerebral ischemia and secondary IS. In the chronic cerebral hypoperfusion (CCH) phase, EE treatment improved behavior performance by alleviating neuronal loss and white matter myelin damage, promoting the expression of brain-derived neurotrophic factor (BDNF) and phosphor-cAMP response element binding protein (p-CREB). Furthermore, infiltration of microglia/macrophages and astrocytes was inhibited, and the levels of IL-1 beta and TNF alpha were decreased. In the IS phase, EE altered the neuronal outcome on day 21 but not on day one after IS. In addition, EE inhibited IS-induced infiltration of microglia/macrophages and astrocytes, mediated the polarization of microglia/macrophages, and reduced pro-inflammatory factors. Importantly, EE improved IS-induced cognitive and motor deficits on day 21. Collectively, our work demonstrates that EE protects mice from cognitive and motor dysfunction and inhibits neuroinflammation caused by CCH and IS.

Automated summary

With the aging of populations, cognitive and motor dysfunction caused by chronic cerebral ischemia and ischemic stroke have become a global problem. Enriched environment (EE) has shown great influence on the brain, and this study investigates its potential effect on cognitive and motor function in mice with chronic cerebral ischemia and secondary stroke (IS). The results show that EE improves behavior performance, reduces neuronal loss and white matter damage, promotes the expression of BDNF and p-CREB, inhibits inflammation, and improves cognitive and motor deficits caused by IS.