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针刺通过激活脑源性神经营养因子/酪氨酸激酶受体B通路改善创伤性脑损伤后的神经功能恢复。

Acupuncture Improved Neurological Recovery after Traumatic Brain Injury by Activating BDNF/TrkB Pathway.

作者信息

Li Xiaohong, Chen Chong, Yang Xiping, Wang Jingjing, Zhao Ming-Liang, Sun Hongtao, Zhang Sai, Tu Yue

机构信息

Institute of Traumatic Brain Injury and Neurology, Pingjin Hospital, Logistics University of Chinese People's Armed Police Forces, Tianjin 300162, China; Key Laboratory of Neurotrauma Repair of Tianjin, Tianjin 300162, China.

出版信息

Evid Based Complement Alternat Med. 2017;2017:8460145. doi: 10.1155/2017/8460145. Epub 2017 Jan 24.

Abstract

How to promote neural repair following traumatic brain injury (TBI) has long been an intractable problem. Although acupuncture has been demonstrated to facilitate the neurological recovery, the underlying mechanism is elusive. Brain-derived neurotrophic factor (BDNF) exerts substantial protective effects for neurological disorders. In this study, we found that the level of BDNF and tropomyosin receptor kinase B (TrkB) was elevated spontaneously after TBI and reached up to the peak at 12 h. Nevertheless, this enhancement is quickly declined to the normal at 48 h. After combined stimulation at the acupoints of Baihui, Renzhong, Hegu, and Zusanli, we found that BDNF and TrkB were still significantly elevated at 168 h. We also observed that the downstream molecular p-Akt and p-Erk1/2 were significantly increased, suggesting that acupuncture could persistently activate the BDNF/TrkB pathway. To further verify that acupuncture improved recovery through activating BDNF/TrkB pathway, K252a (specific inhibitor of TrkB) was treated by injection stereotaxically into lateral ventricle. We observed that K252a could significantly prevent the acupuncture-induced amelioration of motor, sensation, cognition, and synaptic plasticity. These data indicated that acupuncture promoted the recovery of neurological impairment after TBI by activating BDNF/TrkB signaling pathway, providing new molecular mechanism for understanding traditional therapy of acupuncture.

摘要

如何促进创伤性脑损伤(TBI)后的神经修复长期以来一直是一个棘手的问题。尽管针灸已被证明有助于神经功能恢复,但其潜在机制尚不清楚。脑源性神经营养因子(BDNF)对神经疾病具有重要的保护作用。在本研究中,我们发现TBI后BDNF和原肌球蛋白受体激酶B(TrkB)水平自发升高,并在12小时达到峰值。然而,这种升高在48小时迅速下降至正常水平。在百会、人中、合谷和足三里穴位联合刺激后,我们发现BDNF和TrkB在168小时仍显著升高。我们还观察到下游分子p-Akt和p-Erk1/2显著增加,表明针灸可持续激活BDNF/TrkB通路。为了进一步验证针灸通过激活BDNF/TrkB通路改善恢复情况,将K252a(TrkB的特异性抑制剂)立体定向注射到侧脑室。我们观察到K252a可显著阻止针灸诱导的运动、感觉、认知和突触可塑性改善。这些数据表明,针灸通过激活BDNF/TrkB信号通路促进TBI后神经功能障碍的恢复,为理解针灸传统疗法提供了新的分子机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b43b/5294361/5fcf7509ad30/ECAM2017-8460145.001.jpg

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