Evaluating the neuropathogenic CD8 T-cell response following Traumatic Brain Injury using the closed head impact model of engineered rotational acceleration 2270

Abstract Description In traumatic brain injury, the brain is subjected to a series of complex physical forces resulting in primary tissue damage. CD8 T-cells have been implicated in secondary tissue damage in direct blunt-force trauma studies, yet their role in role in rotational-acceleration-induced trauma, commonly observed in motor vehicle accidents or sports-related injuries, is currently unknown. We hypothesize that rotational-acceleration-induced trauma activates neuropathogenic CD8 T-cells. Using an agent that has been shown to modulate CD8 T-cells in other neuroinflammatory disease, we hypothesize that cannabidiol (CBD) can suppress neuroinflammatory CD8 T-cells, thereby reducing neuronal cell death and leading to an improvement in motor, sensory, and cognitive recovery. Rotational-acceleration-based trauma was induced using the closed head impact model of engineered rotational acceleration (CHIMERA) approach. TBI induction was confirmed using the righting reflex assay. Neuroinflammation was evaluated using flow cytometry. CHIMERA-induced mice exhibited a significant increase in the righting reflex time, indicating successful TBI induction. On day 7, we observed 1) an increase in CD8 T-cells in the brain (neuro-infiltration) and 2) an increase in activated CD8 T-cells in the brain (neuro-inflammation), as compared to sham controls. These findings suggest CD8 T-cell involvement in the subacute stage of TBI neuropathology. Future experiments will evaluate CBD attenuation of neuroinflammation. Topic Categories Neuroimmunology (NEUR)