title: Cognitive Deficits and Inflammatory Response Resulting from Mild-to-Moderate Traumatic Brain Injury in Rats Are Exacerbated by Repeated Pre-Exposure to an Innate Stress Stimulus.
abstract: Traumatic brain injury (TBI) is common in both military and civilian populations, and often results in neurobehavioral sequelae that impair quality of life in both patients and their families. Although individuals who are chronically exposed to stress are more likely to experience TBI, it is still unknown whether pre-injury stress influences the outcome after TBI. The present study tested whether behavioral and cognitive long-term outcome after TBI in rats is affected by prior exposure to an innate stress stimulus. Young adult male Sprague-Dawley rats were exposed to the predator odor 2,5-dihydro-2,4,5-trimethylthiazoline (TMT) or to water (WAT); exposure was repeated eight times at irregular intervals over a 2-week period. Rats were subsequently subjected to either mild-to-moderate bilateral brain injury (lateral fluid percussion [LFP]) or sham surgery (Sham). Four experimental groups were studied: Sham-WAT, Sham-TMT, LFP-WAT and LFP-TMT. Compared with Sham-WAT rats, LFP-WAT rats exhibited transient locomotor hyperactivity without signs of anxiety, minor spatial learning acquisition and hippocampal long-term potentiation deficits, and lower baseline activity of the hypothalamic-pituitary-adrenal axis with slightly stronger reactivity to restraint stress. Exposure to TMT had only negligible effects on Sham rats, whereas it exacerbated all deficits in LFP rats except for locomotor hyperactivity. Early brain inflammatory response (8 h post-trauma) was aggravated in rats pre-exposed to TMT, suggesting that increased brain inflammation may sustain functional deficits in these rats. Hence, these data suggest that pre-exposure to stressful conditions can aggravate long-term deficits induced by TBI, leading to severe stress response deficits, possibly due to dysregulated inflammatory response.
authors.affiliation: 1 Institut de Recherche Biomédicale des Armées , Brétigny-sur-Orge, France .|2 Université Claude Bernard Lyon 1 , Bron, France .|3 Institute for Epilepsy , IDÉE, Bron, France .
authors.forename: Michaël
authors.initials: M
authors.lastname: Ogier
authors.affiliation: 2 Université Claude Bernard Lyon 1 , Bron, France .|3 Institute for Epilepsy , IDÉE, Bron, France .
authors.forename: Amor
authors.initials: A
authors.lastname: Belmeguenai
authors.affiliation: 2 Université Claude Bernard Lyon 1 , Bron, France .|3 Institute for Epilepsy , IDÉE, Bron, France .
authors.forename: Thomas
authors.initials: T
authors.lastname: Lieutaud
authors.affiliation: 2 Université Claude Bernard Lyon 1 , Bron, France .|3 Institute for Epilepsy , IDÉE, Bron, France .
authors.forename: Béatrice
authors.initials: B
authors.lastname: Georges
authors.affiliation: 2 Université Claude Bernard Lyon 1 , Bron, France .|3 Institute for Epilepsy , IDÉE, Bron, France .
authors.forename: Sandrine
authors.initials: S
authors.lastname: Bouvard
authors.affiliation: 1 Institut de Recherche Biomédicale des Armées , Brétigny-sur-Orge, France .
authors.forename: Emilie
authors.initials: E
authors.lastname: Carré
authors.affiliation: 1 Institut de Recherche Biomédicale des Armées , Brétigny-sur-Orge, France .|4 Ecole du Val de Grâce , Paris, France .
authors.forename: Frédéric
authors.initials: F
authors.lastname: Canini
authors.affiliation: 2 Université Claude Bernard Lyon 1 , Bron, France .|3 Institute for Epilepsy , IDÉE, Bron, France .
authors.forename: Laurent
authors.initials: L
authors.lastname: Bezin
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D000070642:Brain Injuries, Traumatic / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D060825:Cognitive Dysfunction / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D007249:Inflammation / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D018782:Maze Learning; D051381:Rats; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology
keywords: animal studies; behavioral assessments; cognitive function; inflammation; traumatic brain injury