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

Shehong Zhang; Yonggang Zhang; He Liu; Fengfeng Wu; Zhihong Wang; Liqin Li; Huilian Huang; Sheng Qiu; Yuntao Li

doi:10.3389/fimmu.2023.1114596

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

Front Immunol. 2023 Mar 9:14:1114596. doi: 10.3389/fimmu.2023.1114596. eCollection 2023.

Authors

Shehong Zhang^{1

2}, Yonggang Zhang^{2

3}, He Liu^{2

3}, Fengfeng Wu¹, Zhihong Wang², Liqin Li^{2

3}, Huilian Huang^{2

3}, Sheng Qiu², Yuntao Li^{2

3}

Affiliations

¹ Department of Rehabilitation Medicine, Department of Neurosurgery, Huzhou Central Hospital, Affiliated Huzhou Hospital, Zhejiang University School of Medicine, Huzhou, China.
² Huzhou Key Laboratory of Basic Research and Clinical Translation for Neuromodulation, Huzhou, China.
³ Department of Neurosurgery, Huzhou Central Hospital, Affiliated Huzhou Hospital, Zhejiang University School of Medicine, Huzhou, China.

Abstract

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-1β and TNFα 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.

Keywords: chronic cerebral hypoperfusion; cognitive function; elderly mice; enriched environment; ischemic stroke; neuroinflammation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Brain
Brain Ischemia*
Ischemia / complications
Ischemic Stroke*
Mice
Prognosis

Grants and funding

This work was supported by the Zhejiang Medical and Health Clinical Research and Application Project grant (No. 2022KY360)and the Natural Science Fund Project, Huzhou Science and Technology Bureau (No. 2021YZ01).