中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2014, Vol. 9 ›› Issue (19): 1763-1769.doi: 10.4103/1673-5374.141785

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

脑性瘫痪模型大鼠感觉运动皮质区接受血管内皮生长因子165和神经干细胞移植后的反应

  

  • 收稿日期:2014-07-02 出版日期:2014-10-15 发布日期:2014-10-15
  • 基金资助:

    国家自然科学基金(No. 81070523 and 81270728)

Response of the sensorimotor cortex of cerebral palsy rats receiving transplantation of vascular endothelial growth factor 165-transfected neural stem cells

Jielu Tan, Xiangrong Zheng, Shanshan Zhang, Yujia Yang, Xia Wang, Xiaohe Yu, Le Zhong   

  1. Department of Pediatrics, Xiangya Hospital, Central South University, Changsha, Hunan Province, China
  • Received:2014-07-02 Online:2014-10-15 Published:2014-10-15
  • Contact: Xiangrong Zheng, M.D., Department of Pediatrics, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China, zxr_168@126.com.
  • Supported by:

    This work was supported by grants from the National Natural Science Foundation of China, No. 81070523, 81270728.

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摘要：

实验设想用血管内皮生长因子转染神经干细胞移植脑性瘫痪大鼠可产生神经保护作用。为此，实验将大鼠随机分为假手术组、模型组、磷酸盐缓冲液组、血管内皮生长因子+神经干细胞移植组、单纯神经干细胞移植组5组，后4组均采用左颈总动脉结扎并缺氧处理建立脑性瘫痪大鼠模型，后3组按要求以立体定位仪分别于感觉运动皮质处直接注射磷酸盐缓冲液、血管内皮生长因子165基因+神经干细胞、单纯神经干细胞。通过免疫组织化学染色、水迷宫实验、握持实验和苏木精-伊红染色，观察脑组织病理结构变化后，发现血管内皮生长因子165基因+神经干细胞移植组的模型大鼠脑组织血管内皮生长因子阳性细胞增多，觅水时间和觅水重复次数均减少，握持时间均增多，脑组织细胞变性坏死程度减轻。说明血管内皮生长因子转染神经干细胞移植新生脑性瘫痪大鼠，可减轻其因缺氧缺血所致的脑损伤，改善学习记忆功能，产生神经保护效应。

关键词: 神经再生, 血管内皮生长因子, 神经干细胞, 脑性瘫痪, 动物模型, 移植, 神经保护, 行为测试, 国家自然科学基金

Abstract:

Neural stem cells are characterized by the ability to differentiate and stably express exogenous ge-nes. Vascular endothelial growth factor plays a role in protecting local blood vessels and neurons of newborn rats with hypoxic-ischemic encephalopathy. Transplantation of vascular endothelial growth factor-transfected neural stem cells may be neuroprotective in rats with cerebral palsy. In this study, 7-day-old Sprague-Dawley rats were divided into five groups: (1) sham operation (control), (2) cerebral palsy model alone or with (3) phosphate-buffered saline, (4) vascular endothelial growth factor 165 + neural stem cells, or (5) neural stem cells alone. The cerebral palsy model was established by ligating the left common carotid artery followed by exposure to hypoxia. Phosphate-buffered saline, vascular endothelial growth factor + neural stem cells, and neural stem cells alone were administered into the sensorimotor cortex using the stereotaxic instrument and microsyringe. After transplantation, the radial-arm water maze test and holding test were performed. Immunohistochemistry for vascular endothelial growth factor and histology using hematoxylin-eosin were performed on cerebral cortex. Results revealed that the number of vascular endothelial growth factor-positive cells in cerebral palsy rats transplanted with vascular endothelial growth factor-transfected neural stem cells was increased, the time for finding water and the finding repetitions were reduced, the holding time was prolonged, and the degree of cell degeneration or necrosis was reduced. These findings indicate that the transplantation of vascular endothelial growth factor-transfected neural stem cells alleviates brain damage and cognitive deficits, and is neuroprotective in neonatal rats with hypoxia ischemic-mediated cerebral palsy.

Key words: nerve regeneration, vascular endothelial growth factor, neural stem cells, cerebral palsy, animal model, transplantation, neuroprotection, NSFC grant, neural regeneration