Alcohol-Mediated Cognitive Impairment Following Traumatic Brain Injury: Evidence for Cortical Mitochondrial Dysfunction
Document Type
Article
Publication Date
3-25-2026
Publication Title
Neurotrauma Reports
Abstract
Traumatic brain injury (TBI) and alcohol misuse are major contributors to the global health care burden, both linked to persistent cognitive deficits and mitochondrial dysfunction. This study examined whether post-TBI alcohol exposure exacerbates mitochondrial impairment and contributes to cognitive decline. Adult male Wistar rats were assigned to four groups: Sham, Sham + ethanol (EtOH), TBI, or TBI + EtOH. TBI was induced via lateral fluid percussion 3 days post-craniotomy. Starting 2 days post-injury, EtOH-treated animals received 2.0 g/kg EtOH (i.p.) daily for 5 days. Behavioral testing (Y-maze and open field) was conducted on day 6; brain tissue was collected on day 7 for mitochondrial analysis using the Agilent Seahorse XF Pro Analyzer in the prefrontal cortex (PFC) and retrosplenial cortex (RSC). Rats in the EtOH, TBI, and TBI + EtOH groups showed reduced spontaneous alternation in the Y-maze, suggesting impaired spatial memory. The EtOH group also showed decreased exploratory activity. In the PFC, baseline respiration was unaffected; however, EtOH exposure reduced maximal respiration and glycolytic reserve. In the RSC, TBI and EtOH independently decreased basal respiration, maximal respiration, adenosine triphosphate production, and glycolytic reserve. These findings reveal that alcohol and TBI independently impair mitochondrial bioenergetics in brain regions relevant to cognition and that these deficits parallel behavioral impairments. Disrupted mitochondrial energy metabolism may thus be a key mechanism underlying cognitive dysfunction following TBI and alcohol exposure.
Volume
7
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License
Recommended Citation
Chapa-Dubocq, Xavier R.; Jacotte-Simancas, Alejandra; Martinez-Santana, Andrea; Salling, Michael C.; Simon, Liz; Edwards, Scott; and Molina, Patricia E., "Alcohol-Mediated Cognitive Impairment Following Traumatic Brain Injury: Evidence for Cortical Mitochondrial Dysfunction" (2026). School of Graduate Studies Faculty Publications. 657.
https://digitalscholar.lsuhsc.edu/sogs_facpubs/657
10.1177/2689288X261433371