Environmental enrichment combined with fasudil treatment inhibits neuronal death in the hippocampal CA1 region and ameliorates memory deficits  

作　　者：Gao-Jing Xu Qun Zhang Si-Yue Li Yi-Tong Zhu Ke-Wei Yu Chuan-Jie Wang Hong-Yu Xie Yi Wu 

机构地区：[1]Department of rehabilitation Medicine,Huashan Hospital,Fudan University,Shanghai,China [2]Department of Rehabilitation Medicine,Jinshan Hospital of Fudan University,Shanghai,China

出　　处：《Neural Regeneration Research》2021年第8期1460-1466,共7页中国神经再生研究（英文版）

基　　金：financially supported by the National Natural Science Foundation of China,Nos. 81672242,81972141 (both to YW);Shanghai Municipal Key Clinical Specialty of China,No. shslczdzk02702 (to YW);Shanghai Special Support Plan for High-Level Talents,Yang Fan Funds of China,No. 20YF1403500 (to QZ)。

摘　　要：Currently, no specific treatment exists to promote recovery from cognitive impairment after a stroke. Dysfunction of the actin cytoskeleton correlates well with poststroke cognitive declines, and its reorganization requires proper regulation of Rho-associated kinase(ROCK) proteins. Fasudil downregulates ROCK activation and protects neurons against cytoskeleton collapse in the acute phase after stroke. An enriched environment can reduce poststroke cognitive impairment. However, the efficacy of environmental enrichment combined with fasudil treatment remains poorly understood. A photothrombotic stroke model was established in 6-week-old male C57 BL/6 mice. Twenty-four hours after modeling, these animals were intraperitoneally administered fasudil(10 mg/kg) once daily for 14 successive days and/or provided with environmental enrichment for 21 successive days. After exposure to environmental enrichment combined with fasudil treatment, the number of neurons in the hippocampal CA1 region increased significantly, the expression and proportion of p-cofilin in the hippocampus decreased, and the distribution of F-actin in the hippocampal CA1 region increased significantly. Furthermore, the performance of mouse stroke models in the tail suspension test and step-through passive avoidance test improved significantly. These findings suggest that environmental enrichment combined with fasudil treatment can ameliorate memory dysfunction through inhibition of the hippocampal ROCK/cofilin pathway, alteration of the dynamic distribution of F-actin, and inhibition of neuronal death in the hippocampal CA1 region. The efficacy of environmental enrichment combined with fasudil treatment was superior to that of fasudil treatment alone. This study was approved by the Animal Ethics Committee of Fudan University of China(approval No. 2019-Huashan Hospital JS-139) on February 20, 2019.

关 键 词：cognitive environment HIPPOCAMPUS injury NEUROPROTECTION pathway repair STROKE 

分 类 号：R743.3[医药卫生—神经病学与精神病学]