中国神经再生研究(英文版) ›› 2015, Vol. 10 ›› Issue (10): 1552-1554.doi: 10.4103/1673-5374.165309

• 观点:脑损伤修复保护与再生 • 上一篇    下一篇

烟碱乙酰胆碱受体:有希望成为对创伤性脑损伤神经保护的标靶

  

  • 收稿日期:2015-06-15 出版日期:2015-10-28 发布日期:2015-10-28

Targeting α7 nicotinic acetylcholine receptors: a future potential for neuroprotection from traumatic brain injury

Samuel S. Shin, C. Edward Dixon*   

  1. Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
  • Received:2015-06-15 Online:2015-10-28 Published:2015-10-28
  • Contact: C. Edward Dixon, Ph.D., dixonec@upmc.edu.

摘要:

引发创伤性脑损伤的原因多种多样,如机动车事故、跌倒、暴力和运动相关损伤,这些损伤都会造成认知功能缺陷。对认知障碍的持久后果一直以来都有报道,但其机制尚不明确。胆碱能系统被认为是认知功能的重要调节剂,因此胆碱能功能丧失被认为是是阿尔茨海默病一个重要的触发因素。同样的,创伤性脑损伤诱导的胆碱能系统失调是认知缺陷的显著基本机制之一。最近随着药理学研究的进步发展,已经开发了新型药物靶向胆碱能系统的特定受体亚型。我们对这些试剂在创伤性脑损伤治疗中的可能用途及积极作用进行了讨论。具体地说α7烟碱乙酰胆碱受体已被证实有望用于创伤性脑损伤后神经无损伤和认知功能在阻碍中有重要的作用。这一特定的受体剂的治疗方法有望用于创伤性脑损伤的一种保护策略。

Abstract:

Traumatic brain injury poses a significant socioeconomic burden in the United States. Not only the immediate management for traumatic injury but also the rehabilitation for motor deficits and cognitive impairments amount to tremendous cost of medical care for these individuals. Moreover, the loss of potential human resource among these individuals is innumerable. Since the causes of TBI are varied, such as motor vehicle accident, falls, violence, and sports related injury, the mechanisms of injury are also diverse. However, these injuries all amount to deficits in cognitive functions. The long lasting consequences in cognitive impairments are often under reported and its mechanisms are unclear. Individuals who have suffered TBI in the past have high incidence personality changes and psychiatric issues such as depression, hostility, anxiety disorders, and post traumatic stress disorder. These individuals also have decreased informational processing speed and lower intellectual functioning amounting to difficulty in learning and social interaction.
Cholinergic system is regarded as an important modulator of cognitive function, by its role in learning and memory formation and attention. Thus, in pathologic neurodegenerative diseases such as Alzheimer’s disease (AD), loss of cholinergic functions are believed to be an important contributor to cognitive deficits. Similarly, traumatic brain injury (TBI) induces dysregulation of the cholinergic system, and this is believed to be one of the significant underlying mechanism of cognitive deficits. With recent advancements in pharmacological science, novel agents that target specific receptor subtypes of the cholinergic system have been developed. The possible use and benefits of these agents in TBI will be discussed. Specifically α7 nicotinic acetylcholine receptors have been shown to be major player in both the neuronal injury as well as cognitive dysfunction after TBI. Agents that target these specific receptors are promising potential future targets in both animal studies and clinical trials.