Traumatic brain injury exacerbates alcohol consumption and neuroinflammation with decline in cognition and cholinergic activity.

Abstract

Traumatic brain injury (TBI) is a global health challenge that substantially contributes to disability and is responsible for 30% of injury-related deaths. Annually, over 50 million TBIs occur worldwide, with many adult TBI patients in emergency departments presenting with alcohol in their system. TBI is also a known risk factor for alcohol abuse, yet its interaction with alcohol consumption remains poorly understood. In this study, we demonstrate that the fluid percussion injury (FPI) model of TBI in male C57BL/6 mice significantly increases alcohol consumption and impairs cognitive function. FPI markedly reduced the number and activity of striatal cholinergic interneurons (CINs) while increasing striatal microglial cells. Notably, depleting microglial cells by systemic PLX 5622 administration enhanced cholinergic activity, as measured by electrophysiology and acetylcholine biosensing. These findings suggest that TBI promotes alcohol consumption and impairs cognitive abilities through microglia activation and reduced cholinergic function. This research provides critical insight into the mechanisms linking TBI with increased alcohol use and cognitive deficits, potentially guiding future therapeutic strategies.