中国神经再生研究(英文版) ›› 2022, Vol. 17 ›› Issue (11): 2512-2517.doi: 10.4103/1673-5374.339001

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

基质胶、褪黑素与神经干细胞三维移植体系修复创伤性脑损伤

  

  • 出版日期:2022-11-15 发布日期:2022-04-22
  • 基金资助:
    基金项目(16QNP101);重庆市杰出青年自然科学基金项目(cstc2019jcyjjqX0030)

A three-dimensional matrix system containing melatonin and neural stem cells repairs damage from traumatic brain injury in rats

Xuan-Yu Fang#, Da-Wei Zhao#, Chao Zhang, Hong-Fei Ge, Xu-Yang Zhang, Feng-Chun Zhao, Yi-Bin Jiang, Hua Feng, Rong Hu*   

  1. Department of Neurosurgery and Key Laboratory of Neurotrauma, Southwest Hospital, Army Medical University, Chongqing, China
  • Online:2022-11-15 Published:2022-04-22
  • Contact: Rong Hu, MD, PhD, huchrong@tmmu.edu.cn.
  • Supported by:
    The study was financially supported by the Project, No. 16QNP101 and the Natural Science Foundation for Outstanding Youth of Chongqing, China No. cstc2019jcyjjqX0030 (both to RH).

摘要:

神经干细胞可在病损条件下被激活、增殖和分化,并向损伤区域迁移;但是在创伤性脑损伤后,脑组织缺损以及微环境变化严重影响了神经干细胞的存活以及生长,同时有限的内源性神经干细胞也难以达成损伤区域的修复效果。既往研究以发现褪黑素可促进神经干细胞在氧化应激或缺氧等不利条件下的存活、增殖和分化,因此实验拟探索以褪黑素联合神经干细胞治疗创伤性脑损伤的效果。首先的体外研究证实了褪黑素能在促进氧糖剥夺的神经干细胞的存活。继而以基质胶为基础建立了褪黑素联合神经干细胞三维移植体系,然后以其移植治疗创伤性脑损伤大鼠模型,结果发现与单独基质胶、神经元、基质胶+神经元和基质胶+褪黑素治疗的大鼠相比,这种三维移植体系治疗的大鼠的脑损伤体积较小,存活的神经元的数量更多,神经功能恢复更好。提示以基质胶为基础的褪黑素联合神经干细胞三维移植体系是一种治疗创伤性脑损伤的潜在疗法。

https://orcid.org/0000-0002-6093-9744 (Rong Hu)

关键词: 创伤性脑损伤, 神经干细胞, 褪黑素, 神经功能, 基质胶, 三维移植, 细胞疗法, 磁共振成像

Abstract: Brain lesions can cause neural stem cells to activate, proliferate, differentiate, and migrate to the injured area. However, after traumatic brain injury, brain tissue defects and microenvironment changes greatly affect the survival and growth of neural stem cells; the resulting reduction in the number of neural stem cells impedes effective repair of the injured area. Melatonin can promote the survival, proliferation, and differentiation of neural stem cells under adverse conditions such as oxidative stress or hypoxia that can occur after traumatic brain injury. Therefore, we investigated the therapeutic effects of melatonin combined with neural stem cells on traumatic brain injury in rats. First, in vitro studies confirmed that melatonin promoted the survival of neural stem cells deprived of oxygen and glucose. Then, we established a three-dimensional Matrigel-based transplantation system containing melatonin and neural stem cells and then used it to treat traumatic brain injury in rats. We found that treatment with the Matrigel system containing melatonin and neural stem cells decreased brain lesion volume, increased the number of surviving neurons, and improved recovery of neurological function compared with treatment with Matrigel alone, neural stem cells alone, Matrigel and neural stem cells combined, and Matrigel and melatonin combined. Our findings suggest that the three-dimensional Matrigel-based transplantation system containing melatonin and neural stem cells is a potential treatment for traumatic brain injury.

Key words: cell therapy, magnetic resonance imaging, Matrigel, melatonin, neural stem cells, neurological function recovery, three-dimensional transplantation, traumatic brain injury