中国神经再生研究(英文版) ›› 2016, Vol. 11 ›› Issue (6): 951-956.doi: 10.4103/1673-5374.184494

• 原著:周围神经损伤修复保护与再生 • 上一篇    下一篇

正中神经电刺激促创伤性脑损伤昏迷后觉醒的机制

  

  • 收稿日期:2016-05-20 出版日期:2016-06-30 发布日期:2016-06-30
  • 基金资助:

    中国国家自然科学基金项目(81260295);江西省自然科学基金项目(20132BAB205063)

Mechanisms responsible for the effect of median nerve electrical stimulation on traumatic brain injury-induced coma: orexin-A-mediated N-methyl-D-aspartate receptor subunit NR1 upregulation

Zhen Feng*, #, Qing Du#   

  1. Department of Rehabilitation, the First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China
  • Received:2016-05-20 Online:2016-06-30 Published:2016-06-30
  • Contact: Zhen Feng, fengzhenly@sina.com.
  • Supported by:

    This study was supported by the National Natural Science Foundation of China, No. 81260295; the Natural Science Foundation of Jiangxi Province of China, No. 20132BAB205063.

摘要:

我们既往研究显示,正中神经电刺激能明显增强创伤性脑损伤昏迷大鼠前额皮质中orexin-A及其受体1的表达,符合正中神经电刺激有助于促进觉醒的相关研究结果。为进一步了解正中神经电刺激促觉醒的机制,我们分析了创伤性脑损伤昏迷大鼠经正中神经电刺激后的觉醒及N-甲基-D-天冬氨酸受体亚基NR1的动态变化。Western blot和免疫组化染色结果显示,创伤性脑损伤昏迷大鼠前额皮质中N-甲基-D-天冬氨酸受体亚基NR1的表达随时间延长而增加,且给予30 Hz,0.5 ms,1.0 mA,15 min正中神经电刺激,可促进N-甲基-D-天冬氨酸受体亚基NR1的表达,且苏醒大鼠数量增加,而侧脑室注射orexin-A受体1拮抗剂SB334867可降低这种影响。故作者认为正中神经电刺激可能通过上调orexin-A介导N-甲基-D-天冬氨酸受体亚基NR1的表达,从而促进了创伤性脑损伤昏迷的觉醒。 

orcid: 0000-0002-6268-2516 (Zhen Feng)

关键词: 神经再生, NR1, 正中神经电刺激, 创伤性脑损伤, 昏迷, 失眠, Orexin-A, 前额皮质

Abstract:

Electrical stimulation of the median nerve is a noninvasive technique that facilitates awakening from coma. In rats with traumatic brain injury- induced coma, median nerve stimulation markedly enhances prefrontal cortex expression of orexin-A and its receptor, orexin receptor 1. To further understand the mechanism underlying wakefulness mediated by electrical stimulation of the median nerve, we evaluated its effects on the expression of the N-methyl-D-aspartate receptor subunit NR1 in the prefrontal cortex in rat models of traumatic brain injury-induced coma, using immunohistochemistry and western blot assays. In rats with traumatic brain injury, NR1 expression increased with time after injury. Rats that underwent electrical stimulation of the median nerve (30 Hz, 0.5 ms, 1.0 mA for 15 minutes) showed elevated NR1 expression and greater recovery of consciousness than those without stimulation. These effects were reduced by intracerebroventricular injection of the orexin receptor 1 antagonist SB334867. Our results indicate that electrical stimulation of the median nerve promotes recovery from traumatic brain injury-induced coma by increasing prefrontal cortex NR1 expression via an orexin-A-mediated pathway.

Key words: nerve regeneration, NR1, median nerve electrical stimulation, traumatic brain injury, coma, wakefulness, orexin-A, prefrontal cortex, neural regeneration