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Very early environmental enrichment protects against apoptosis and improves functional recovery from hypoxic-ischemic brain injury

Authors
 Hoo Young Lee  ;  Suk-Young Song  ;  Jihye Hwang  ;  Ahreum Baek  ;  Dawoon Baek  ;  Sung Hoon Kim  ;  Jung Hyun Park  ;  Sungchul Choi  ;  Soonil Pyo  ;  Sung-Rae Cho 
Citation
 FRONTIERS IN MOLECULAR NEUROSCIENCE, Vol.15 : 1019173, 2023-02 
Journal Title
FRONTIERS IN MOLECULAR NEUROSCIENCE
Issue Date
2023-02
Keywords
Fas ; apoptosis ; environmental enrichment ; neuroprotection ; stroke ; voluntary exercise
Abstract
Appropriate rehabilitation of stroke patients at a very early phase results in favorable outcomes. However, the optimal strategy for very early rehabilitation is at present unclear due to the limited knowledge on the effects of very early initiation of rehabilitation based on voluntary exercise (VE). Environmental enrichment (EE) is a therapeutic paradigm for laboratory animals that involves complex combinations of physical, cognitive, and social stimuli, as well as VE. Few studies delineated the effect of EE on apoptosis in very early stroke in an experimental model. Although a minimal benefit of early rehabilitation in stroke models has been claimed in previous studies, these were based on a forced exercise paradigm. The aim of this study is to determine whether very early exposure to EE can effectively regulate Fas/FasL-mediated apoptosis following hypoxic-ischemic (HI) brain injury and improve neurobehavioral function. C57Bl/6 mice were housed for 2 weeks in either cages with EE or standard cages (SC) 3 h or 72 h after HI brain injury. Very early exposure to EE was associated with greater improvement in motor function and cognitive ability, reduced volume of the infarcted area, decreased mitochondria-mediated apoptosis, and decreased oxidative stress. Very early exposure to EE significantly downregulated Fas/FasL-mediated apoptosis, decreased expression of Fas, Fas-associated death domain, cleaved caspase-8/caspase-8, cleaved caspase-3/caspase-3, as well as Bax and Bcl-2, in the cerebral cortex and the hippocampus. Delayed exposure to EE, on the other hand, failed to inhibit the extrinsic pathway of apoptosis. This study demonstrates that very early exposure to EE is a potentially useful therapeutic translation for stroke rehabilitation through effective inhibition of the extrinsic and intrinsic apoptotic pathways.
Files in This Item:
T202301690.pdf Download
DOI
10.3389/fnmol.2022.1019173
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Rehabilitation Medicine (재활의학교실) > 1. Journal Papers
Yonsei Authors
Park, Jung Hyun(박중현) ORCID logo https://orcid.org/0000-0003-3262-7476
Cho, Sung-Rae(조성래) ORCID logo https://orcid.org/0000-0003-1429-2684
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/193741
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