中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2021, Vol. 16 ›› Issue (12): 2512-2520.doi: 10.4103/1673-5374.313048

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

丰富环境联合法舒地尔可促进缺血性脑卒中后运动功能恢复和轴突再生

  

  • 出版日期:2021-12-15 发布日期:2021-05-15
  • 基金资助:
    国家自然科学基金项目（81672242，81972141）；上海市青年科技英才扬帆计划（20YF1403500）；上海市重点临床专科（shslczdzk02702

Environmental enrichment combined with fasudil promotes motor function recovery and axonal regeneration after stroke

Yi-Tong Zhu, Qun Zhang, Hong-Yu Xie, Ke-Wei Yu, Gao-Jing Xu, Si-Yue Li, Yi Wu*   

  1. Department of Rehabilitation Medicine, Huashan Hospital, Fudan University, Shanghai, China
  • Online:2021-12-15 Published:2021-05-15
  • Contact: Yi Wu, PhD, wuyi@fudan.edu.cn.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, Nos. 81672242 (to YW), 81972141 (to YW); Shanghai Sailing Program, No. 20YF1403500 (to QZ); and Shanghai Municipal Key Clinical Specialty of China, No. shslczdzk02702 (to YW).

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摘要：

ROCK抑制剂法舒地尔对中枢神经系统具有保护作用。丰富环境可诱导缺血性脑卒中模型运动障碍的恢复，两者联合应用是否可更有效促进脑卒中后运动功能恢复和皮质轴突再生？实验通过光栓塞左侧感觉运动皮质诱导建立缺血性脑卒中小鼠模型，造模后1-21d每天腹腔注射10 mg/kg法舒地尔，造模第7-21天进行丰富环境干预。结果发现，丰富环境联合法舒地尔可有效改善小鼠的运动功能，并增加梗死侧大脑皮质中生长相关蛋白43的表达以及健侧轴突的再生，并明显下调ROCK，p-LIMK1和p-Cofilin的表达，且效果优于单独丰富环境或法舒地尔干预。结果提示丰富环境联合法舒地尔可部分通过刺激轴突再生来促进脑卒中后运动恢复，其机制与调控ROCK/LIMK1/Cofilin通路有关。实验于2016年2月24日经复旦大学动物伦理委员会批准（批准号20160858A232）。

https://orcid.org/0000-0003-4854-9898 (Yi Wu)

https://orcid.org/0000-0003-3393-6733 (Yi-Tong Zhu)

关键词: 丰富环境, 法舒地尔, 缺血性脑卒中, 运动恢复, 轴突再生, 生物素化葡聚糖胺, 尼氏小体, 生长相关蛋白43, ROCK/LIMK1/Cofilin通路

Abstract: Fasudil, a Rho-associated protein kinase (ROCK) inhibitor, has a protective effect on the central nervous system. In addition, environmental enrichment is a promising technique for inducing the recovery of motor impairments in ischemic stroke models. The present study aimed to explore whether environmental enrichment combined with fasudil can facilitate motor function recovery and induce cortical axonal regeneration after stroke. First, a mouse model of ischemic cerebral stroke was established by photochemical embolization of the left sensorimotor cortex. Fasudil solution (10 mg/kg per day) was injected intraperitoneally for 21 days after the photothrombotic stroke. An environmental enrichment intervention was performed on days 7–21 after the photothrombotic stroke. The results revealed that environmental enrichment combined with fasudil improved motor function, increased growth-associated protein 43 expression in the infarcted cerebral cortex, promoted axonal regeneration on the contralateral side, and downregulated ROCK, p-LIM domain kinase (LIMK)1, and p-cofilin expression. The combined intervention was superior to monotherapy. These findings suggest that environmental enrichment combined with fasudil treatment promotes motor recovery after stroke, at least partly by stimulating axonal regeneration. The underlying mechanism might involve ROCK/LIMK1/cofilin pathway regulation. This study was approved by the Institutional Animal Care and Use Committee of Fudan University, China (approval No. 20160858A232) on February 24, 2016. 

Key words: axon regeneration, biotinylated dextran amines, environmental enrichment, fasudil, growth-associated protein 43, ischemic stroke, motor recovery, Nissl bodies, Rho/ROCK pathway

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