中国神经再生研究(英文版) ›› 2014, Vol. 9 ›› Issue (19): 1745-1752.doi: 10.4103/1673-5374.143417

• 原著:颅神经损伤修复保护与再生 • 上一篇    下一篇

亚低温与神经干细胞移植共同对抗缺血缺氧性脑病:叠加的神经保护效应

  

  • 收稿日期:2014-09-15 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(81271382)

Mild hypothermia combined with neural stem cell transplantation for hypoxic-ischemic encephalopathy: neuroprotective effects of combined therapy

Lin Wang, Feng Jiang, Qifeng Li, Xiaoguang He, Jie Ma   

  1. Department of Pediatric Neurosurgery, Xinhua Hospital of Shanghai Jiaotong University, Shanghai 200092, China
  • Received:2014-09-15 Online:2014-10-15 Published:2014-10-15
  • Contact: Jie Ma, Ph.D., M.D., Department of Pediatric Neurosurgery, Xinhua Hospital of Shanghai Jiaotong University, Shanghai 200092, China, majie365@hotmail.com.
  • Supported by:

    This work was supported by the National Natural Science Foundation of China, No. 81271382.

摘要:

神经干细胞移植可用于治疗缺血性脑卒中,但移植后神经干细胞的在缺血缺氧大脑的微环境中常出现凋亡。实验设想以亚低温(27–28 °C)的神经保护作用增强神经干细胞移植(1.0×105 /μL)治疗缺血缺氧性脑病新生小鼠对移植细胞的存活率,并观察对实验小鼠远期神经功能产生的影响。发现亚低温联合神经干细胞移植治疗的缺血缺氧性脑病模型小鼠,大脑皮质与海马区域相关炎症因子核转录因子κB和凋亡因子caspase 3的表达降低,脑坏死容积减小,移植的神经干细胞存活率较高,神经功能障碍明显改善,其效果优于单独应用亚低温或神经干细胞移植治疗。结果说明亚低温联合神经干细胞移植保护缺氧缺血性脑病的作用可能通过抗炎和抗凋亡的多重途径的叠加效应而实现的。

关键词: 神经再生, 脑损伤, 缺氧缺血性脑病, 神经前体细胞, 亚低温, 神经干细胞, 细胞移植, 海马, 神经元, 细胞凋亡, 星形胶质细胞, 少突胶质细胞, 神经保护, 国家自然科学基金

Abstract:

Neural stem cell transplantation is a useful treatment for ischemic stroke, but apoptosis often occurs in the hypoxic-ischemic environment of the brain after cell transplantation. In this study, we determined if mild hypothermia (27–28°C) can increase the survival rate of neural stem cells (1.0 × 105 /μL) transplanted into neonatal mice with hypoxic-ischemic encephalopathy. Long-term effects on neurological functioning of the mice were also examined. After mild hypothermia combined with neural stem cell transplantation, we observed decreased expression levels of inflammatory factor nuclear factor-kappa B and apoptotic factor caspase-3, reduced cerebral infarct volumes, increased survival rate of transplanted cells, and marked improvements in neurological function. Thus, the neuroprotective effects of mild hypothermia combined with neural stem cell transplantation are superior to those of monotherapy. Moreover, our findings suggest that the neuroprotective effects of mild hypothermia combined with neural stem cell transplantation on hypoxic-ischemic encephalopathy are achieved by anti-inflammatory and anti-apoptotic mechanisms.

Key words: nerve regeneration, brain injury, hypoxic-ischemic encephalopathy, neural precursor cells, hypothermia, neural stem cells, cell transplantation, hippocampus, neuron, cell apoptosis, astrocytes, oligodendrocytes, neuroprotection, NSFC grants, neural regeneration