PI: Neal Simon
Co-PI(s): Angela Brown, Hugo Caram
University: Lehigh University
Industry partner: Azevan Pharmaceuticals
Traumatic brain injuries represent a major public health problem. About 2.7 million Americans per year suffer these injuries. Mild TBIs (mTBI; concussions) account for 85% of these and more than 2.2 million Emergency Room (ER) visits annually (1). This figure is likely an underestimate of the mTBI annual rate because not all head impact injuries lead to an ER or primary care physician visit. These mild head injuries result from multiple causes, including falls, car accidents, and sports participation, and can be single (mTBI) or repetitive (rmTBI). Although the effects of mTBIs were thought to rapidly resolve, it is now recognized that they can result in a post-concussion syndrome that lasts at least a month in more than half of patients, a year in some 40% of cases, and increase the long-term risk of neurodegenerative disease (2,3). The biomedical community is highly interested in cellular changes after these injuries (4). These changes can potentially serve as biomarkers that can be used to improve diagnostics and as endpoints for assessing treatment response. The proposed preclinical studies will test two potential TBI biomarkers: Iba1, a biomarker for neuroinflammation and longer-term injury risk, and AQP4, a water channel protein that is acutely dysregulated in TBIs and indicates blood-brain barrier compromise, an injury-induced change that is strongly linked to cerebral edema, another risk factor associated with these injuries. The proposed preclinical studies will examine the intracellular expression and localization of Iba-1 and AQP4 in targeted brain regions using immunocytochemical methods after single and repetitive mild TBI induction. Positive results of the proposed studies will provide new, high-value data that provide the potential basis for a novel approach to diagnostic PET and MRI scans for mild TBIs. The development and use of biomarkers for the detection of and assessment of interventions can improve health outcomes by determining the extent of brain injury and the effectiveness of drugs or other treatment strategies.