Investigation of the Effect of Androgen Receptor Knockout on Pathophysiology of Traumatic Brain Injury

Traumatic brain injury (TBI) has affected approximately 10 million people every year and has become an important global health issue worldwide. Published literature has shown that TBI is the leading cause of injury-induced deaths. Severe TBI often leads to death or loss of working and/or self-caring ability. It is a tremendous burden to care the TBI patients losing self-caring ability for their caring family members and the nation’s Health Care System. Therefore, TBI has attracted the attention of neuroscientists, physicians and researchers and has become the most imperative medical problem to be solved. Androgen has been demonstrated to exert a beneficial effect on injured neurons and TBI patients. Androgen receptor is widely thought to mediate the various effects of androgen. However, the role of androgen receptor involved in the mechanisms underlying TBI remains to be elucidated. Our Central Hypothesis is that androgen exercises a protective effect on neurons against traumatic brain injury through its binding with androgen receptor and knockout of androgen receptor exacerbates TBI. In the previous grant, we have shown that TBI increases the expression of autophagy markers and glial fibrillary acidic protein (GFAP) and deletion of androgen receptor further enhances their expression. Recent evidence indicates that knockdown of collapsin response mediator protein 2 (CRMP2) reduces the glutamate-induced neuronal death. This finding has led us to propose that CRMP2 plays an important role in the pathophysiology of TBI. In this grant proposal, we will extend our previous grant and further investigate if TBI influences the expression of CRMP2 and if deletion of androgen receptor affects the expression of CRMP2 following TBI and the motor performance of TBI mice using the androgen receptor knockout (ARKO) mice. The eventual aim of this grant is to pave the way leading to the development of innovative therapeutic agents or strategies for treating TBI by understanding the complex pathophysiology of TBI.