Post‐injury alcohol exposure exacerbates neuroinflammation and impairs neurological recovery following traumatic brain injury (859.6)

Abstract

BACKGROUND: There are ~1.7 million reported traumatic brain injury (TBI) cases in the U.S. annually. Alcohol abuse contributes to 36% to 51% of all TBI incidents, and patients continue to use alcohol after TBI in up to 26% of cases. Limited preclinical studies have examined the impact of post‐injury alcohol exposure on TBI recovery and the underlying mechanisms. The aim of this study was to determine the effect of post‐injury alcohol exposure on TBI outcomes in terms of neuropathological and neurological recovery.METHODS: Male Sprague‐Dawley rats (~300 g) were fitted with a female Luer‐lock over a 5 mm left lateral craniotomy 1 week prior to injury. TBI was induced by lateral fluid percussion (~30 PSI, ~25 ms) under isoflurane anesthesia. At day 4 post‐injury, animals were exposed to either intermittent alcohol vapor (95% ethanol 14h on /10h off) or room air for 10 days. RESULTS: TBI produced immediate apnea (17±5 s) and delayed righting reflex (419±30 s). Neurological severity score (NSS) was increased as a result of injury prior to alcohol exposure (2‐fold; p<0.05). TBI/Air group showed progressive recovery with no significant impairment in NSS detected at 14 and 18 days post‐TBI. In contrast, alcohol exposure impaired recovery and had higher NSS than time‐matched air‐exposed animals throughout the 10 day period of alcohol exposure and following a 4 day abstinence period (3.5‐fold; p<0.05). Alcohol exposure alone increased NSS score after 10 days of vapor, but returned to baseline after 4 days of abstinence. Immunofluorescence revealed increased activation of astrocytes, microglia, and other markers of neuroinflammation in alcohol exposed brains after TBI.CONCLUSIONS: These findings indicate that alcohol exposure impairs neurological recovery, which may be caused by sustained neuroinflammation. The clinical implications of long‐term consequences in TBI patients exposed to alcohol during recovery warrant further investigation.Grant Funding Source: Supported by NIAAA‐AA7577, F30AA022838