中国神经再生研究(英文版) ›› 2022, Vol. 17 ›› Issue (7): 1556-1565.doi: 10.4103/1673-5374.330611

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

电针对脑缺血小鼠病灶周脑组织神经胶质抗原2阳性细胞的影响

  

  • 出版日期:2022-07-15 发布日期:2022-01-17
  • 基金资助:

    韩国国家研究基金会(NRF)的基础科学研究计划的支持(2018R1A2A2A05018926

Effects of electroacupuncture on the functionality of NG2-expressing cells in perilesional brain tissue of mice following ischemic stroke

Hong Ju Lee1, 2, Da Hee Jung1, 2, Nam Kwen Kim3, Hwa Kyoung Shin1, 2, Byung Tae Choi1, 2, *   

  1. 1Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan, Republic of Korea; 2Graduate Training Program of Korean Medicine for Healthy Aging, Pusan National University, Yangsan, Republic of Korea; 3Department of Korean Ophthalmology, Otolaryngology and Dermatology, School of Korean Medicine, Pusan National University, Yangsan, Republic of Korea
  • Online:2022-07-15 Published:2022-01-17
  • Contact: Byung Tae Choi, PhD, choibt@pusan.ac.kr.
  • Supported by:
    This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), which was funded by the Ministry of Science, ICT, and Future Planning (2018R1A2A2A05018926) (to BTC).

摘要:

神经胶质抗原2(NG2)阳性细胞在脑缺血条件下具有多能干细胞的特性。实验观察了电针四神聪穴治疗对脑缺血小鼠病灶周脑组织NG2阳性细胞及运动功能的影响。电针改善了脑缺血小鼠的运动障碍,且1 mA比3 mA的电针刺激或自由基清除剂依达拉奉的阳性对照治疗更有效果。1 mA的电针通过减少肿瘤坏死因子α的表达提高了病灶周围脑组织中NG2阳性细胞的存活率。电针上调了神经营养因子,如脑源性神经营养因子、肿瘤生长因子β和神经营养素3的表达。在病灶周围的纹状体,电针明显使少突胶质细胞、内皮细胞和小胶质细胞/巨噬细胞标记物CC1、CD31和CD68和NG2双标阳性细胞的数量增加。电针也明显激活了脑源性神经营养因子/tropomyosin受体激酶B和糖原合酶激酶3β信号。结果表明,电针可能通过激活脑源性神经营养因子相关信号,促进NG2的细胞的存活和分化,从而改善脑缺血小鼠的运动功能。

https://orcid.org/0000-0002-5965-4346 (Byung Tae Choi)

Abstract: Neural/glial antigen 2 (NG2)-expressing cells has multipotent stem cell activity under cerebral ischemia. Our study examined the effects of electroacupuncture (EA) therapy (2 Hz, 1 or 3 mA, 20 minutes) at the Sishencong acupoint on motor function after ischemic insult in the brain by investigating the rehabilitative potential of NG2-derived cells in a mouse model of ischemic stroke. EA stimulation alleviated motor deficits caused by ischemic stroke, and 1 mA EA stimulation was more efficacious than 3 mA EA stimulation or positive control treatment with edaravone, a free radical scavenger. The properties of NG2-expressing cells were altered with 1 mA EA stimulation, enhancing their survival in perilesional brain tissue via reduction of tumor necrosis factor alpha expression. EA stimulation robustly activated signaling pathways related to proliferation and survival of NG2-expressing cells and increased the expression of neurotrophic factors such as brain-derived neurotrophic factor, tumor growth factor beta, and neurotrophin 3. In the perilesional striatum, EA stimulation greatly increased the number of NG2-expressing cells double-positive for oligodendrocyte, endothelial cell, and microglia/macrophage markers (CC1, CD31, and CD68). EA therapy also greatly activated brain-derived neurotrophic factor/tropomyosin receptor kinase B and glycogen synthase kinase 3 beta signaling. Our results indicate that EA therapy may prevent functional loss at the perilesional site by enhancing survival and differentiation of NG2-expressing cells via the activation of brain-derived neurotrophic factor -induced signaling, subsequently ameliorating motor dysfunction. The animal experiments were approved by the Animal Ethics Committee of Pusan National University (approval Nos. PNU2019-2199 and PNU2019-2884) on April 8, 2019 and June 19, 2019.

Key words: brain-derived neurotrophic factor, differentiation, electroacupuncture, motor function, neural/glial antigen 2, perilesional striatum, stroke, survival