Traumatic brain injury (TBI) is the major global health issue and has been estimated to be the leading cause of death by 2020 worldwide. Evidence has shown that approximately 10 million people suffer from TBI every year. Severe TBI commonly causes death or disability, which requires long-term care - a gigantic financial burden on the TBI patients, the caring family members and the National Healthcare System. Thus, TBI has become one of the major health issues to be resolved. Numerous lines of evidence have shown that androgens have a favorable effect on injured neurons and TBI patients. It is generally accepted that androgen receptor mediates the effect of androgens. Nonetheless, the role of androgen receptor in the pathophysiology of TBI remains unclear. A recent study points out that inhibition of collapsin response mediator protein 2 (CRMP2) attenuates the glutamate-induced neuronal death. Our previous findings show that TBI induces the expression of glial fibrillary acidic protein (GFAP), a biomarker of TBI, and the expression of cleaved CRMP2 and knockout of androgen receptor further enhances the TBI-induced expression of GFAP and the cleaved CRMP2. In this grant proposal, we will further assess the impact of androgen receptor knockout on the pathophysiology of TBI. We will evaluate if TBI affects the expression of phosphorylation of cleaved CRMP2 (p-c-CRMP2) and if deletion of androgen receptor further promotes the TBI-induced expression of p-c-CRMP2. Moreover, we will test if deletion of androgen receptor further aggravates the TBI-induced brain edema. Our preliminary data showed that TBI induced the expression of p-c-CRMP2 and androgen receptor knockout further increased the TBI-induced expression of p-c-CRMP2. Our preliminary data also indicated that glutamate caused the death of C6 glioma cells and induced the expression of phosphorylation of cleaved CRMP2. Moreover, our preliminary results showed that the brain water content was significantly higher in male mice with deletion of androgen receptor (ARKO) than in male control littermates, suggesting that androgen receptor knockout exacerbates brain edema. Our results derived from this grant will undoubtedly promote our understanding of the role of androgen receptor in the pathophysiology of TBI and may ultimately pave the way to the development of novel therapeutic treatments for TBI.
|Effective start/end date||8/1/14 → 7/31/15|
- Traumatic brain injury Androgen receptor knockout Androgens p-c-CRMP2 Brain edema
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