Understanding the role of traumatic brain injury in ALS

This proposal aims to understand the link between traumatic brain injury (TBI) and cortical defects in ALS. Recent studies suggest that TBI and repeated concussions are related to high incidence of ALS in athletes and war veterans. Pathology in both cases involves a strong immune response. Therefore, we hypothesize that upper motor neuron (a.k.a. corticospinal motor neuron, CSMN) degeneration might be a consequence of an aggravated immune response in the motor cortex. A novel mouse model of TBI to understand the relation between TBI, ALS, and CSMN death will be developed using a reporter mouse line in which CSMN are fluorescently labeled. TBI will be implemented by controlled cortical impact (CCI) over the motor cortex and CSMN degeneration will be confirmed via different parameters including morphological and behavioral studies. The link between the innate and adaptive immunity and CSMN degeneration will be elucidated by implementing TBI in healthy and ALS reporter mouse model in which immune cells are genetically labeled with red and green fluorescence. This proposal will reveal the overall immunological landscape with respect to TBI, CSMN degeneration, and ALS by developing a novel model system.