title: Alcohol exposure after mild focal traumatic brain injury impairs neurological recovery and exacerbates localized neuroinflammation.
abstract: Traumatic brain injury (TBI) represents a leading cause of morbidity and mortality among young individuals. Alcohol abuse is a risk factor associated with increased TBI incidence. In addition, up to 26% of TBI patients engage in alcohol consumption after TBI. Limited preclinical studies have examined the impact of post-injury alcohol exposure on TBI recovery. The aim of this study was to determine the isolated and combined effects of TBI and alcohol on cognitive, behavioral, and physical recovery, as well as on associated neuroinflammatory changes. Male Sprague-Dawley rats (∼300g) were subjected to a mild focal TBI by lateral fluid percussion (∼30PSI, ∼25ms) under isoflurane anesthesia. On day 4 after TBI, animals were exposed to either sub-chronic intermittent alcohol vapor (95% ethanol 14h on/10h off; BAL∼200mg/dL) or room air for 10days. TBI induced neurological dysfunction reflected by an increased neurological severity score (NSS) showed progressive improvement in injured animals exposed to room air (TBI/air). In contrast, TBI animals exposed to alcohol vapor (TBI/alcohol) showed impaired NSS recovery throughout the 10-day period of alcohol exposure. Open-field exploration test revealed an increased anxiety-like behavior in TBI/alcohol group compared to TBI/air group. Additionally, alcohol-exposed animals showed decreased locomotion and impaired novel object recognition. Immunofluorescence showed enhanced reactive astrocytes, microglial activation, and HMGB1 expression localized to the injured cortex of TBI/alcohol as compared to TBI/air animals. The expression of neuroinflammatory markers showed significant positive correlation with NSS. These findings indicated a close relationship between accentuated neuroinflammation and impaired neurological recovery from post-TBI alcohol exposure. The clinical implications of long-term consequences in TBI patients exposed to alcohol during recovery warrant further investigation.
authors.affiliation: Department of Physiology and Alcohol and Drug Abuse Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, LA 70112, United States.
authors.forename: Sophie X
authors.initials: SX
authors.lastname: Teng
authors.affiliation: Department of Physiology and Alcohol and Drug Abuse Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, LA 70112, United States.
authors.forename: Paige S
authors.initials: PS
authors.lastname: Katz
authors.affiliation: Department of Physiology and Alcohol and Drug Abuse Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, LA 70112, United States.
authors.forename: John K
authors.initials: JK
authors.lastname: Maxi
authors.affiliation: Department of Physiology and Alcohol and Drug Abuse Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, LA 70112, United States.
authors.forename: Jacques P
authors.initials: JP
authors.lastname: Mayeux
authors.affiliation: Department of Physiology and Alcohol and Drug Abuse Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, LA 70112, United States.
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Gilpin
authors.affiliation: Department of Physiology and Alcohol and Drug Abuse Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, LA 70112, United States. Electronic address: pmolin@lsuhsc.edu.
authors.forename: Patricia E
authors.initials: PE
authors.lastname: Molina
mesh_terms: D000428:Alcohol Drinking / Q000276:immunology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D001930:Brain Injuries / Q000276:immunology* / Q000503:physiopathology; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000276:immunology / Q000293:injuries / Q000473:pathology; D053331:Ectodysplasins / Q000187:drug effects / Q000276:immunology; D000431:Ethanol / Q000494:pharmacology*; D005106:Exploratory Behavior / Q000187:drug effects* / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000187:drug effects / Q000276:immunology; D024243:HMGB1 Protein / Q000187:drug effects / Q000276:immunology; D007249:Inflammation; D051381:Rats; D017207:Rats, Sprague-Dawley; D021641:Recognition, Psychology / Q000187:drug effects* / Q000502:physiology; D020127:Recovery of Function / Q000187:drug effects*; D015599:Trauma Severity Indices
chemical_list: D002492:Central Nervous System Depressants; D053331:Ectodysplasins; C506019:Eda protein, mouse; D005904:Glial Fibrillary Acidic Protein; D024243:HMGB1 Protein; C582808:HMGB1 protein, mouse; D000431:Ethanol
keywords: Alcohol; Neurobehavior; Neuroinflammation; Traumatic brain injury