Very early environmental enrichment protects against apoptosis and improves functional recovery from hypoxic–ischemic brain injury
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)...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-02-01
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| Series: | Frontiers in Molecular Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnmol.2022.1019173/full |
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| author | Hoo Young Lee Hoo Young Lee Hoo Young Lee Suk-Young Song Jihye Hwang Jihye Hwang Ahreum Baek Ahreum Baek Dawoon Baek Dawoon Baek Sung Hoon Kim Jung Hyun Park Jung Hyun Park Sungchul Choi Soonil Pyo Soonil Pyo Sung-Rae Cho Sung-Rae Cho Sung-Rae Cho Sung-Rae Cho |
| author_facet | Hoo Young Lee Hoo Young Lee Hoo Young Lee Suk-Young Song Jihye Hwang Jihye Hwang Ahreum Baek Ahreum Baek Dawoon Baek Dawoon Baek Sung Hoon Kim Jung Hyun Park Jung Hyun Park Sungchul Choi Soonil Pyo Soonil Pyo Sung-Rae Cho Sung-Rae Cho Sung-Rae Cho Sung-Rae Cho |
| author_sort | Hoo Young Lee |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-10T16:51:58Z |
| format | Article |
| id | doaj.art-61275dd28f044a97be5bc12837645c9f |
| institution | Directory Open Access Journal |
| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-04-10T16:51:58Z |
| publishDate | 2023-02-01 |
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| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-61275dd28f044a97be5bc12837645c9f2023-02-07T13:58:13ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992023-02-011510.3389/fnmol.2022.10191731019173Very early environmental enrichment protects against apoptosis and improves functional recovery from hypoxic–ischemic brain injuryHoo Young Lee0Hoo Young Lee1Hoo Young Lee2Suk-Young Song3Jihye Hwang4Jihye Hwang5Ahreum Baek6Ahreum Baek7Dawoon Baek8Dawoon Baek9Sung Hoon Kim10Jung Hyun Park11Jung Hyun Park12Sungchul Choi13Soonil Pyo14Soonil Pyo15Sung-Rae Cho16Sung-Rae Cho17Sung-Rae Cho18Sung-Rae Cho19Department of Rehabilitation Medicine, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Republic of KoreaNational Traffic Injury Rehabilitation Hospital, Gyeonggi-do, Republic of KoreaYonsei University College of Medicine, Seoul, Republic of KoreaGraduate Program of Biomedical Engineering, Yonsei University College of Medicine, Seoul, Republic of KoreaGraduate Program of Biomedical Engineering, Yonsei University College of Medicine, Seoul, Republic of KoreaDepartment and Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul, Republic of KoreaDepartment and Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul, Republic of KoreaDepartment of Rehabilitation Medicine, Yonsei University Wonju College of Medicine, Wonju, Republic of KoreaDepartment and Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul, Republic of KoreaDepartment of Rehabilitation Medicine, Yonsei University Wonju College of Medicine, Wonju, Republic of KoreaDepartment of Rehabilitation Medicine, Yonsei University Wonju College of Medicine, Wonju, Republic of KoreaYonsei University College of Medicine, Seoul, Republic of KoreaDepartment of Rehabilitation Medicine, Rehabilitation Institute of Neuromuscular Disease, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of KoreaYonsei University College of Medicine, Seoul, Republic of KoreaNeuracle Science Co. Ltd., Seoul, Republic of KoreaBrain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, Republic of KoreaGraduate Program of Biomedical Engineering, Yonsei University College of Medicine, Seoul, Republic of KoreaDepartment and Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul, Republic of KoreaBrain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, Republic of Korea0Rehabilitation Institute of Neuromuscular Disease, Yonsei University College of Medicine, Seoul, Republic of KoreaAppropriate 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.https://www.frontiersin.org/articles/10.3389/fnmol.2022.1019173/fullenvironmental enrichmentvoluntary exercisestrokeapoptosisFasneuroprotection |
| spellingShingle | Hoo Young Lee Hoo Young Lee Hoo Young Lee Suk-Young Song Jihye Hwang Jihye Hwang Ahreum Baek Ahreum Baek Dawoon Baek Dawoon Baek Sung Hoon Kim Jung Hyun Park Jung Hyun Park Sungchul Choi Soonil Pyo Soonil Pyo Sung-Rae Cho Sung-Rae Cho Sung-Rae Cho Sung-Rae Cho Very early environmental enrichment protects against apoptosis and improves functional recovery from hypoxic–ischemic brain injury Frontiers in Molecular Neuroscience environmental enrichment voluntary exercise stroke apoptosis Fas neuroprotection |
| title | Very early environmental enrichment protects against apoptosis and improves functional recovery from hypoxic–ischemic brain injury |
| title_full | Very early environmental enrichment protects against apoptosis and improves functional recovery from hypoxic–ischemic brain injury |
| title_fullStr | Very early environmental enrichment protects against apoptosis and improves functional recovery from hypoxic–ischemic brain injury |
| title_full_unstemmed | Very early environmental enrichment protects against apoptosis and improves functional recovery from hypoxic–ischemic brain injury |
| title_short | Very early environmental enrichment protects against apoptosis and improves functional recovery from hypoxic–ischemic brain injury |
| title_sort | very early environmental enrichment protects against apoptosis and improves functional recovery from hypoxic ischemic brain injury |
| topic | environmental enrichment voluntary exercise stroke apoptosis Fas neuroprotection |
| url | https://www.frontiersin.org/articles/10.3389/fnmol.2022.1019173/full |
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