Traumatic Brain Injury Exacerbates Alcohol Consumption and Neuroinflammation with Decline in Cognition and Cholinergic Activity

Traumatic Brain Injury Exacerbates Alcohol Consumption and Neuroinflammation with Decline in Cognition and Cholinergic Activity | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Traumatic Brain Injury Exacerbates Alcohol Consumption and Neuroinflammation with Decline in Cognition and Cholinergic Activity Jun Wang, Himanshu Gangal, Jaclyn Iannucci, Yufei Huang, Ruifeng Chen, and 11 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4966070/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 16 Oct, 2025 Read the published version in Translational Psychiatry → Version 1 posted 11 You are reading this latest preprint version Abstract Traumatic brain injury (TBI) is a global health challenge, responsible for 30% of injury-related deaths and significantly contributing to disability. Annually, over 50 million TBIs occur worldwide, with most adult patients at emergency departments showing 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 mice significantly increases alcohol consumption and impairs cognitive function. At cellular levels, FPI markedly reduced the number and activity of striatal cholinergic interneurons (CINs) while increasing microglial cells. Notably, depleting microglial cells provided neuroprotection, mitigating cholinergic loss and enhancing cholinergic activity. These findings suggest that TBI may promote alcohol consumption and impair cognitive abilities through microglia activation and consequently reduced cholinergic function. Our research provides critical insights into the mechanisms linking TBI with increased alcohol use and cognitive deficits, potentially guiding future therapeutic strategies. Health sciences/Diseases Biological sciences/Neuroscience Fluid percussion injury alcohol consumption cognitive ability striatum microglia cholinergic interneurons acetylcholine. Full Text Additional Declarations The authors have declared there is NO conflict of interest to disclose Supplementary Files Gangal3cMS20240609Supplementary.pdf Cite Share Download PDF Status: Published Journal Publication published 16 Oct, 2025 Read the published version in Translational Psychiatry → Version 1 posted Unknown event 01 Mar, 2025 Editorial decision: Reject after peer review 19 Dec, 2024 Review # 2 received at journal 25 Oct, 2024 Reviewer # 3 agreed at journal 15 Oct, 2024 Reviewer # 2 agreed at journal 06 Oct, 2024 Review # 1 received at journal 30 Sep, 2024 Reviewer # 1 agreed at journal 09 Sep, 2024 Reviewers invited by journal 05 Sep, 2024 Editor assigned by journal 05 Sep, 2024 Submission checks completed at journal 27 Aug, 2024 First submitted to journal 23 Aug, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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