中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2018, Vol. 13 ›› Issue (2): 244-251.doi: 10.4103/1673-5374.226395

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

迷走神经电刺激对脑损伤大鼠的促醒机制：上调前额叶皮质中orexin A和Orexins1受体蛋白的表达？

  

  • 收稿日期:2017-12-25 出版日期:2018-02-15 发布日期:2018-02-15
  • 基金资助:

    国家自然科学基金(81260295)和中国研究生创新基金（YC 2015-S 090）

Wake-promoting effects of vagus nerve stimulation after traumatic brain injury: upregulation of orexin-A and orexin receptor type 1 expression in the prefrontal cortex

Xiao-yang Dong, Zhen Feng   

  1. Department of Rehabilitation Medicine, the First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China
  • Received:2017-12-25 Online:2018-02-15 Published:2018-02-15
  • Contact: Zhen Feng,fengzhenly@sina.com.
  • Supported by:

    This study was supported by the Natural Science Foundation of China, No. 81260295 and the Graduate Student Innovation Fund of Jiangxi Province of China, No. YC2015-S090.

PDF

318

摘要：

Orexins是下丘脑外侧区分泌的一种重要的神经肽，与睡眠觉醒周期密切相关，其在大脑分布区与迷走神经在大脑的投射区部分重合。有研究表明，迷走神经电刺激可减少脑创伤癫痫患者的嗜睡时间和快动眼睡眠周期。为此，实验拟观察电刺激迷走神经是否具有昏迷促醒的效果，并探讨其机制是否与Oreinxs有关。实验以“自由落体”打击法建立创伤性脑损伤大鼠模型设为TBI组，造模后立即电刺激迷走神经(频率30 Hz，电流1.0 mA，脉冲持续时间0.5 ms，总刺激时间15 min)设为电刺激组，造模后立即进行侧脑室注射Orexins1受体(OX1R)拮抗剂SB334867，然后给予迷走神经电刺激设为拮抗剂组，观察各组大鼠电刺激后的意识状态变化，并通过ELISA、Western blot和免疫组织化学技术检测各组前额叶皮质与睡眠觉醒周期密切相关的Orexin A和OX1R蛋白表达发现，与TBI组相比，电刺激组脑创伤昏迷大鼠的意识状态明显改善，其前额叶Orexin-A Orexin-A蛋白表达在TBI后24 h内逐渐增高，而OX1R蛋白表达及免疫反应在TBI后12 h达到高峰。与电刺激组相比，拮抗剂组电刺激迷走神经的促醒效果(意识状态恢复)差，前额叶Orexin-A蛋白及OX1R受体蛋白及免疫反应均下调。上述数据表明，迷走神经电刺激能够改善脑创伤昏迷大鼠的意识状态，上调前额叶orexin-A和OX1R蛋白表达与促醒机制可能有关。

orcid:0000-0003-0134-465X(Zhen Feng)

关键词: 神经再生, 脑损伤, Orexin-A, OX1R, 迷走神经电刺激, 脑创伤, 促醒, 昏迷, 觉醒, 前额叶, 神经再生, 神经递质

Abstract:

Orexins, produced in the lateral hypothalamus, are important neuropeptides that participate in the sleep/wake cycle, and their expression coincides with the projection area of the vagus nerve in the brain. Vagus nerve stimulation has been shown to decrease the amounts of daytime sleep and rapid eye movement in epilepsy patients with traumatic brain injury. In the present study, we investigated whether vagus nerve stimulation promotes wakefulness and affects orexin expression. A rat model of traumatic brain injury was established using the free fall drop method. In the stimulated group, rats with traumatic brain injury received vagus nerve stimulation (frequency, 30 Hz;current, 1.0 mA; pulse width, 0.5 ms; total stimulation time, 15 minutes). In the antagonist group, rats with traumatic brain injury were intracerebroventricularly injected with the orexin receptor type 1 (OX1R) antagonist SB334867 and received vagus nerve stimulation.Changes in consciousness were observed after stimulation in each group. Enzyme-linked immunosorbent assay, western blot assay and immunohistochemistry were used to assess the levels of orexin-A and OX1R expression in the prefrontal cortex. In the stimulated group,consciousness was substantially improved, orexin-A protein expression gradually increased within 24 hours after injury and OX1R expression reached a peak at 12 hours, compared with rats subjected to traumatic brain injury only. In the antagonist group, the wake-promoting effect of vagus nerve stimulation was diminished, and orexin-A and OX1R expression were decreased, compared with that of the stimulated group. Taken together, our findings suggest that vagus nerve stimulation promotes the recovery of consciousness in comatose rats after traumatic brain injury. The upregulation of orexin-A and OX1R expression in the prefrontal cortex might be involved in the wake-promoting effects of vagus nerve stimulation.

Key words: nerve regeneration, brain injury, orexin-A, orexin receptor type 1, vagus nerve stimulation, traumatic brain injury, wake-promoting, coma, wakefulness, prefrontal cortex, neurotransmitter, neural regeneration