Zhang Yi, Liu Wen, Liu Lingling, Liu Yang, Yang Youqing, Yang Zhijie, Chen Xiuping
Department of Rehabilitation Medicine, The 1st Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.
Traditional Chinese Medicine Department, The 1st Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.
Brain Res Bull. 2025 Sep;229:111459. doi: 10.1016/j.brainresbull.2025.111459. Epub 2025 Jul 11.
This study aimed to examine the effects of preconditioning with an enriched environment (EE) on neuroplasticity following cerebral ischemia-reperfusion (I/R) injury and to elucidate its underlying neuroprotective mechanisms. While prior research has indicated that EE preconditioning may mitigate neuronal apoptosis, the molecular pathways contributing to neuroplasticity enhancement post-I/R injury remain insufficiently characterized.
Male Sprague-Dawley rats were allocated into three experimental groups: (1) Middle cerebral artery occlusion (MCAO) with pre-ischemic EE exposure (PIEE), (2) pre-ischemic standard condition (SC) exposure with MCAO (PISC), and (3) pre-ischemic SC exposure with sham surgery (Sham). Neurological function and infarct volume were assessed three days post-MCAO. The expression levels of neuroplasticity-related proteins, including neurofilament (NF), synaptophysin (Syn), and microtubule-associated protein 2 (MAP-2), as well as neurotrophic factors such as nerve growth factor (NGF) and basic fibroblast growth factor (bFGF), were analyzed using western blot and immunohistochemical techniques. Correlation analyses were conducted to evaluate the relationship between protein expression and neurological outcomes.
Compared to the PISC group, the PIEE group demonstrated significant improvements in neurological function and reduced infarct volumes. Expression levels of NF, Syn, and MAP-2 were elevated in the ischemic penumbra cortex in the PIEE group. Additionally, EE preconditioning resulted in increased expression of NGF and bFGF. These molecular changes were positively correlated with functional recovery in the MCAO model.
Pre-ischemic exposure to an enriched environment may enhance neuroplasticity and support functional recovery following cerebral I/R injury, potentially through the upregulation of neuroplasticity-associated proteins and neurotrophic factors. These findings support the development of EE-based interventions for ischemic stroke prevention and rehabilitation.
本研究旨在探讨丰富环境（EE）预处理对脑缺血再灌注（I/R）损伤后神经可塑性的影响，并阐明其潜在的神经保护机制。虽然先前的研究表明EE预处理可能减轻神经元凋亡，但I/R损伤后促进神经可塑性增强的分子途径仍未得到充分表征。
将雄性Sprague-Dawley大鼠分为三个实验组：（1）缺血前暴露于丰富环境（PIEE）的大脑中动脉闭塞（MCAO）组，（2）缺血前暴露于标准条件（SC）并进行MCAO的组（PISC），以及（3）缺血前暴露于SC并进行假手术的组（假手术组）。在MCAO术后三天评估神经功能和梗死体积。使用蛋白质印迹和免疫组织化学技术分析神经可塑性相关蛋白的表达水平，包括神经丝（NF）、突触素（Syn）和微管相关蛋白2（MAP-2），以及神经营养因子如神经生长因子（NGF）和碱性成纤维细胞生长因子（bFGF）。进行相关性分析以评估蛋白表达与神经学结果之间的关系。
与PISC组相比，PIEE组的神经功能有显著改善，梗死体积减小。PIEE组缺血半暗带皮质中NF、Syn和MAP-2的表达水平升高。此外，EE预处理导致NGF和bFGF的表达增加。这些分子变化与MCAO模型中的功能恢复呈正相关。
缺血前暴露于丰富环境可能增强神经可塑性，并支持脑I/R损伤后的功能恢复，可能是通过上调神经可塑性相关蛋白和神经营养因子实现的。这些发现支持开发基于EE的干预措施用于缺血性中风的预防和康复。
