Acute Alcohol Intoxication is Associated With Sustained Neuroinflammation Without Exacerbation of Early Neurobehavioral Outcomes Post Traumatic Brain Injury

Abstract

Approximately 1.7 million people sustain a traumatic brain injury (TBI) annually, and acute alcohol intoxication (AAI) contributes to 36% to 51% of TBI incidents in the U.S. Studies indicate that the risk of injury is positively correlated with blood alcohol concentrations (BAC). However, conflicting reports from animal and clinical studies have failed to establish whether AAI significantly impacts outcomes from TBI. The aim of the study was to determine whether AAI aggravates neurobehavioral and neuroinflammatory sequelae from TBI. Male Sprague‐Dawley rats were surgically instrumented with gastric and vascular catheters prior to fitting with a female Luer‐lock over a 5 mm left lateral craniotomy. After a 3 day recovery, animals received a primed (2.5 g/kg) 15 h constant (300 mg/kg/h) intragastric alcohol infusion achieving BAC of 266±10 mg/dl. TBI was induced by lateral fluid percussion (~1.4J, ~30 ms) 30 minutes following discontinuation of the infusion. AAI at the time of TBI did not alter apnea duration (15.3±5.3 sec vs. 26.5±8 sec), righting reflex (716±118 vs. 522±83), and neurobehavioral outcomes (neurological Δ2.2+0.6 vs. Δ3.9+0.6; behavioral Δ1.7+0.8 vs. Δ1.3+0.1 scores). TBI resulted in a localized inflammatory response reflected in increased myeloperoxidase (MPO) activity in the ipsilateral (10‐fold; p<0.05) cortex 24 h post‐TBI in dextrose treated animals. AAI did not alter MPO activity but markedly exacerbated neuroinflammation as reflected by significantly (P<0.05) higher IL‐1, IL‐6, TNFα, and MCP‐1 mRNA expression as compared to the dextrose‐treated animals at 24 h post‐TBI. These results show dissociation between neuroinflammation and clinical neurobehavioral measures following TBI in AAI. The clinical implications of enhanced neuroinflammation to long term recovery in the AAI TBI victim warrant further investigation.