Effect of prior exposure to enriched environment on cellular apoptosis after experimental stroke
Effect of prior exposure to enriched environment on cellular apoptosis after experimental stroke
复制标题
先前暴露于丰富环境对实验性脑卒中后细胞凋亡的影响
DOI：
10.1007/s11033-022-07494-y
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发表时间：
2022-05-04
影响因子：
2.8
通讯作者：
Zhang, Xin
中科院分区：
文献类型：
--
作者：
Chen, Xiuping;Zhang, Xin
背景越来越多的证据，包括我们以前的研究，已经证明脑缺血/再灌注(I/R)损伤后丰富的环境(EE)可以促进大鼠神经功能的恢复。然而，在损伤前暴露EE是否在中风中起到神经保护作用的研究很少。在这项研究中，我们研究了预先暴露于EE对大鼠脑I/R损伤后的神经保护作用和潜在的抗细胞凋亡作用。方法与结果大鼠在EE或标准条件下饲养4周后，随机分为右侧大脑中动脉闭塞(MCAO)120min组和假手术组。根据居住环境和手术方式，将大鼠分为3组：缺血前EE+MCAO组(PIE)、缺血前SC+MCAO组(PISC)和缺血前SC+假手术组(Sham)。手术后48小时，对大鼠进行了一系列评估。我们发现，预先暴露于EE可以改善功能结果，减少梗塞体积，并减轻组织学损害。PIPE组缺血半暗带皮质细胞凋亡数减少，P53、PUMA、Bax、AIF表达水平降低。PieE组与PISC组相比，Bcl2、HSP70蛋白表达增强。PIPE治疗还显著提高了缺血半暗带的BDNF水平。此外，抑制细胞凋亡和上调BDNF的表达水平与改善MCAO大鼠的功能恢复有关。结论EE预适应可抑制MCAO大鼠半暗带区细胞凋亡，上调BDNF的表达，这可能有助于卒中后神经功能的恢复。
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.