Xiuping Chen1, Xin Zhang2. 1. Department of Rehabilitation Medicine, The First Affiliated Hospital of Nanchang University, 17 Yongwai Street, Nanchang, 330006, Jiangxi, China. 2. Department of Rehabilitation Medicine, Zhongnan Hospital of Wuhan University, 169 Donghu Street, Wuhan, 430071, Hubei, China. zhangxin0439@whu.edu.cn.
Abstract
BACKGROUND: Growing evidence, including our previous studies, has demonstrated that an enriched environment (EE) after cerebral ischemia/reperfusion (I/R) injury improves neurofunctional recovery in rats. However, whether EE exposure prior to injury could play a neuroprotective role in stroke has seldom been investigated. In this study, we examined the neuroprotective effects of prior exposure to EE and investigated the potential anti-apoptotic effect in rats after cerebral I/R injury. METHODS AND RESULTS: Rats were housed in EE or standard conditions (SC) for four weeks and then randomly assigned to receive 120 min of right middle cerebral occlusion (MCAO) or sham operation. Based on the housing environment and the procedure they underwent, the rats were divided into the following three groups: preischemic EE + MCAO (PIEE), preischemic SC + MCAO (PISC) and preischemic SC + sham-operated (sham). Forty-eight hours after the operation, the rats were subjected to a series of assessments. We found that prior exposure to EE improved functional outcomes, reduced infarct volume and attenuated histological damage. The apoptotic cell numbers in the ischemic penumbra cortex decreased in PIEE group, as did the p53, PUMA, Bax and AIF expression levels. The protein expression of Bcl-2 and HSP70 was increased in the PIEE group compared with the PISC group. PIEE treatment also significantly increased the BDNF level in the ischemic penumbra. In addition, inhibition of cell apoptosis and upregulation of BDNF expression levels were correlated with the improved functional recovery of MCAO rats. CONCLUSIONS: These findings suggest that EE preconditioning inhibited cell apoptosis and upregulated BDNF expression in the penumbra of MCAO rats, which may contribute to neurofunctional recovery after stroke.
BACKGROUND: Growing evidence, including our previous studies, has demonstrated that an enriched environment (EE) after cerebral ischemia/reperfusion (I/R) injury improves neurofunctional recovery in rats. However, whether EE exposure prior to injury could play a neuroprotective role in stroke has seldom been investigated. In this study, we examined the neuroprotective effects of prior exposure to EE and investigated the potential anti-apoptotic effect in rats after cerebral I/R injury. METHODS AND RESULTS: Rats were housed in EE or standard conditions (SC) for four weeks and then randomly assigned to receive 120 min of right middle cerebral occlusion (MCAO) or sham operation. Based on the housing environment and the procedure they underwent, the rats were divided into the following three groups: preischemic EE + MCAO (PIEE), preischemic SC + MCAO (PISC) and preischemic SC + sham-operated (sham). Forty-eight hours after the operation, the rats were subjected to a series of assessments. We found that prior exposure to EE improved functional outcomes, reduced infarct volume and attenuated histological damage. The apoptotic cell numbers in the ischemic penumbra cortex decreased in PIEE group, as did the p53, PUMA, Bax and AIF expression levels. The protein expression of Bcl-2 and HSP70 was increased in the PIEE group compared with the PISC group. PIEE treatment also significantly increased the BDNF level in the ischemic penumbra. In addition, inhibition of cell apoptosis and upregulation of BDNF expression levels were correlated with the improved functional recovery of MCAO rats. CONCLUSIONS: These findings suggest that EE preconditioning inhibited cell apoptosis and upregulated BDNF expression in the penumbra of MCAO rats, which may contribute to neurofunctional recovery after stroke.
Authors: Connie W Tsao; Aaron W Aday; Zaid I Almarzooq; Alvaro Alonso; Andrea Z Beaton; Marcio S Bittencourt; Amelia K Boehme; Alfred E Buxton; April P Carson; Yvonne Commodore-Mensah; Mitchell S V Elkind; Kelly R Evenson; Chete Eze-Nliam; Jane F Ferguson; Giuliano Generoso; Jennifer E Ho; Rizwan Kalani; Sadiya S Khan; Brett M Kissela; Kristen L Knutson; Deborah A Levine; Tené T Lewis; Junxiu Liu; Matthew Shane Loop; Jun Ma; Michael E Mussolino; Sankar D Navaneethan; Amanda Marma Perak; Remy Poudel; Mary Rezk-Hanna; Gregory A Roth; Emily B Schroeder; Svati H Shah; Evan L Thacker; Lisa B VanWagner; Salim S Virani; Jenifer H Voecks; Nae-Yuh Wang; Kristine Yaffe; Seth S Martin Journal: Circulation Date: 2022-01-26 Impact factor: 39.918