中国神经再生研究(英文版) ›› 2015, Vol. 10 ›› Issue (2): 277-285.doi: 10.4103/1673-5374.152383

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

成年缺血性脑损伤大鼠大脑皮质确实可出现内源性神经发生:但大部分细胞难以成熟

  

  • 收稿日期:2014-10-13 出版日期:2015-02-17 发布日期:2015-02-17

Cortical neurogenesis in adult rats after ischemic brain injury: most new neurons fail to mature

Qing-quan Li 1, Guan-qun Qiao 1, Jun Ma 1, Hong-wei Fan 2, Ying-bin Li 1   

  1. 1 Department of Neurosurgery, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
    2 Department of Neurosurgery, the First Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
  • Received:2014-10-13 Online:2015-02-17 Published:2015-02-17
  • Contact: Ying-bin Li, Ph.D., yixinntu@foxmail.com.

摘要:

为验证缺血性脑损伤后内源性神经祖细胞可从损伤大脑新皮质中分离分化为神经元或神经胶质细胞参与损伤后神经再生的假设,实验发现成年大鼠脑缺血再灌注损伤后1,3d,大鼠大脑皮质中出现nestin/sox-2双阳性神经祖细胞,且nestin/sox-2双阳性神经祖细胞也呈胶质纤维酸性蛋白阳性。损伤后3,7d,大鼠大脑皮质中出现DCX/BrdU双阳性新生不成熟神经元;损伤后14d,大鼠大脑皮质中出现微管相关蛋白2/BrdU双阳性新生半成熟神经元;损伤后28d,大鼠大脑皮质中出现少量NeuN/BrdU双阳性成熟神经元。同时脑缺血损伤后大脑皮质中发现胶质纤维酸性蛋白/BrdU双阳性星形胶质细胞。结果证明成年大鼠缺血性损伤大脑皮质中确实可出现神经祖细胞,且其能够分化为星形胶质细胞和神经元样细胞,但大部分难以成熟。

关键词: 神经再生, 大脑中动脉闭塞, 脑损伤, 神经元, 星形胶质细胞, 少突胶质细胞, 神经祖细胞, 增殖, 分化, 神经发生

Abstract:

The present study examines the hypothesis that endogenous neural progenitor cells isolated from the neocortex of ischemic brain can differentiate into neurons or glial cells and contribute to neural regeneration. We performed middle cerebral artery occlusion to establish a model of cerebral ischemia/reperfusion injury in adult rats. Immunohistochemical staining of the cortex 1, 3, 7, 14 or 28 days after injury revealed that neural progenitor cells double-positive for nestin and sox-2 appeared in the injured cortex 1 and 3 days post-injury, and were also positive for glial fibrillary acidic protein. New neurons were labeled using bromodeoxyuridine and different stages of maturity were identified using doublecortin, microtubule-associated protein 2 and neuronal nuclei antigen immunohistochemistry. Immature new neurons coexpressing doublecortin and bromodeoxyuridine were observed in the cortex at 3 and 7 days post-injury, and semi-mature and mature new neurons double-positive for microtubule-associated protein 2 and bromodeoxyuridine were found at 14 days post-injury. A few mature new neurons coexpressing neuronal nuclei antigen and bromodeoxyuridine were observed in the injured cortex 28 days post-injury. Glial fibrillary acidic protein/bromodeoxyuridine double-positive astrocytes were also found in the injured cortex. Our findings suggest that neural progenitor cells are present in the damaged cortex of adult rats with cerebral ischemic brain injury, and that they differentiate into astrocytes and immature neurons, but most neurons fail to reach the mature stage.

Key words: nerve regeneration, middle cerebral artery occlusion, brain injury, neurons, astrocytes,    , oligodendrocytes, neural progenitor cells, proliferation, differentiation, neurogenesis, neural regeneration