Identification of Novel Therapeutic Targets for Traumatic Brain Injury by Proteomic Analysis of Response to Injury in APOE3 and APOE4 Transgenic Mice

摘要

Brain injury due to trauma (traumatic brain injury or TBI) is a significant cause of mortality and both acute and chronic morbidity, particularly in military personnel. Two over-arching issues must be addressed before effective pharmacologic treatments can be developed for TBI. Firstly, peripheral biomarkers reflecting the degree and nature of injury need to be elucidated. Secondly, the molecular cascades that lead to neuronal damage and death need to be fully quantitatively and qualitatively understood with a view to finding target molecules suitable for pharmacotherapy. We are using state of the art proteomic approaches to analyze the brain tissue from mouse models of TBI administered using the controlled cortical impact (CCI) procedure. In order to maximize the discrimination between recovery outcomes these studies are being carried out on APOE3 and APOE4 transgenic mice, which demonstrate relatively favorable and unfavorable outcomes respectively, following TBI. As APOE genotype is key in determining the clinical consequences of TBI, injury- dependent changes in protein expression in brain tissue expressing apoE3 versus apoE4 will be expected to correlate with outcome.