中国神经再生研究(英文版) ›› 2023, Vol. 18 ›› Issue (9): 1976-1982.doi: 10.4103/1673-5374.363835

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

CXC趋化因子受体7增强缺血性脑卒中后的神经可塑性

  

  • 出版日期:2023-09-15 发布日期:2023-03-06
  • 基金资助:
    中国国家自然科学基金项目(81401002,81801053)

C-X-C chemokine receptor type 7 antibody enhances neural plasticity after ischemic stroke

Xiao-Qian Zhang1, Xiao-Yin Wang1, Bing-Chao Dong1, Mei-Xuan Li1, Yu Wang1, Ting Xiao2, Shan-Shan Zhao1, *   

  1. 1Department of Neurology, The First Hospital of China Medical University, Shenyang, Liaoning Province, China; 2Key Laboratory of Immunodermatology, Ministry of Health, Ministry of Education, Shenyang, Liaoning Province, China
  • Online:2023-09-15 Published:2023-03-06
  • Contact: Shan-Shan Zhao, PhD, zhaoshsh826@hotmail.com.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, Nos. 81401002 (to SSZ), and 81801053 (to XQZ).

摘要:

基质细胞衍生因子1及其受体CXC趋化因子受体4可调节脑卒中后的神经再生,但其另一种广泛分布于发育和成年的中枢神经系统的受体CXC趋化因子受体7是否也参与神经再生,目前尚不可知。实验通过大脑皮质和纹状体注射内皮素1制作局灶性脑缺血大鼠模型,从损伤后第7天开始,连续6d通过微量给药系统向侧脑室内注射CXC趋化因子受体7中和抗体。结果显示,CXC趋化因子受体7抗体能增加脑缺血大鼠发芽皮质脊髓束纤维的总长度和数量,促进去神经支配脊髓突触标志物囊泡谷氨酸转运体和生长相关蛋白43的表达,促进纹状体中少突胶质细胞祖细胞的分化和成熟。此外,CXC趋化因子受体7抗体还能增加纹状体中CXC趋化因子受体4的表达,激活 RAS/ERK 信号通路相关蛋白RAS和ERK1/2的表达,并改善大鼠运动功能。提示CXC趋化因子受体7可通过促进轴突再生、突触发生以及髓鞘再生,改善缺血性脑卒中后神经功能的恢复,且这一作用可能通过激活CXC趋化因子受体4以及激活RAS/ERK1/2信号通路实现的。

https://orcid.org/0000-0002-9785-2861 (Shan-Shan Zhao)

关键词: CXC趋化因子受体7 抗体, 脑缺血, 脑卒中, 基质细胞衍生因子1, CXC趋化因子受体4, RAS, 细胞外信号调节激酶, 神经可塑性, 轴突再生, 突触再生, 髓鞘再生

Abstract: Stromal cell-derived factor-1 and its receptor C-X-C chemokine receptor 4 (CXCR4) have been shown to regulate neural regeneration after stroke. However, whether stromal cell-derived factor-1 receptor CXCR7, which is widely distributed in the developing and adult central nervous system, participates in neural regeneration remains poorly understood. In this study, we established rat models of focal cerebral ischemia by injecting endothelin-1 into the cerebral cortex and striatum. Starting on day 7 after injury, CXCR7-neutralizing antibody was injected into the lateral ventricle using a micro drug delivery system for 6 consecutive days. Our results showed that CXCR7-neutralizing antibody increased the total length and number of sprouting corticospinal tract fibers in rats with cerebral ischemia, increased the expression of vesicular glutamate transporter 1 and growth-related protein 43, markers of the denervated spinal cord synapses, and promoted the differentiation and maturation of oligodendrocyte progenitor cells in the striatum. In addition, CXCR7 antibody increased the expression of CXCR4 in the striatum, increased the protein expression of RAS and ERK1/2 associated with the RAS/ERK signaling pathway, and improved rat motor function. These findings suggest that CXCR7 improved neural functional recovery after ischemic stroke by promoting axonal regeneration, synaptogenesis, and myelin regeneration, which may be achieved by activation of CXCR4 and the RAS/ERK1/2 signaling pathway. 

Key words: axonal regeneration, cerebral ischemia, C-X-C chemokine receptor 4, CXCR7 antibody, neural plasticity, RAS/ERK pathway, remyelination, stroke, stromal cell-derived factor-1, synaptogenesis