Traumatic Brain Injury and Ethanol Exposure Differentially Disrupt Mitochondrial Function in the Retrosplenial Cortex of Female Rats

Traumatic brain injury (TBI), a leading cause of long-term neurological disability, imposes high energetic demands for neural recovery, a process critically dependent on mitochondrial function. Chronic alcohol exposure also perturbs mitochondrial metabolism, exacerbating neural vulnerability. Although both insults independently impair mitochondrial activity, their combined impact on recovery and energy regulation in females remains unclear. This study assessed the effects of TBI and sub-chronic ethanol (EtOH) vapor exposure on mitochondrial bioenergetics and behavior in the retrosplenial cortex (RSC), a brain region essential for working memory. Adult female Wistar rats (n=12/group) were assigned to Sham, Sham+EtOH, TBI, or TBI+EtOH groups. Four days post-surgery, EtOH-exposed animals underwent ten days of vapor exposure targeting ~200 mg/dL blood alcohol levels. Behavioral testing (open field and spontaneous alternation) was conducted six hours after the final EtOH session, during early withdrawal. RSC tissue was collected 24 hours later for mitochondrial respiration analysis using Seahorse respirometry. TBI resulted in a ~5% body weight loss (p< 0.05) within six days post-injury, while EtOH exposure led to a ~4% reduction after achieving target blood alcohol levels. The TBI+EtOH group exhibited a sustained ~6% loss (p< 0.05). Basal respiration in the RSC decreased by 38% with EtOH (p< 0.01) and 33% with TBI (p< 0.05) compared to control. Maximal respiration declined by ~32–33% in both TBI and EtOH groups (p< 0.001). Combined TBI+EtOH exposure did not produce additive effects. Non-mitochondrial oxygen consumption increased by ~39% following TBI (p=0.056). Both TBI and EtOH independently reduced mitochondrial respiration without additive deficits, suggesting overlapping mechanisms underlying bioenergetic vulnerability. The elevated non-mitochondrial oxygen consumption after TBI may indicate compensatory shifts in oxygen utilization. Ongoing studies aim to expand sample size to strengthen these findings. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.