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.