title: Mild head injury increasing the brain's vulnerability to a second concussive impact.
abstract: OBJECTIVE
  Mild, traumatic repetitive head injury (RHI) leads to neurobehavioral impairment and is associated with the early onset of neurodegenerative disease. The authors developed an animal model to investigate the behavioral and pathological changes associated with RHI.
  
  
  METHODS
  Adult male C57BL/6 mice were subjected to a single injury (43 mice), repetitive injury (two injuries 24 hours apart; 49 mice), or no impact (36 mice). Cognitive function was assessed using the Morris water maze test, and neurological motor function was evaluated using a battery of neuroscore, rotarod, and rotating pole tests. The animals were also evaluated for cardiovascular changes, blood-brain barrier (BBB) breakdown, traumatic axonal injury, and neurodegenerative and histopathological changes between 1 day and 56 days after brain trauma. No cognitive dysfunction was detected in any group. The single-impact group showed mild impairment according to the neuroscore test at only 3 days postinjury, whereas RHI caused pronounced deficits at 3 days and 7 days following the second injury. Moreover, RHI led to functional impairment during the rotarod and rotating pole tests that was not observed in any animal after a single impact. Small areas of cortical BBB breakdown and axonal injury. observed after a single brain injury, were profoundly exacerbated after RHI. Immunohistochemical staining for microtubule-associated protein-2 revealed marked regional loss of immunoreactivity only in animals subjected to RHI. No deposits of beta-amyloid or tau were observed in any brain-injured animal.
  
  
  CONCLUSIONS
  On the basis of their results, the authors suggest that the brain has an increased vulnerability to a second traumatic insult for at least 24 hours following an initial episode of mild brain trauma.
authors.affiliation: The Head Injury Center, Department of Neurosurgery, University of Pennsylvania School of Medicine, Philadelphia 19104-6316, USA.
authors.forename: H L
authors.initials: HL
authors.lastname: Laurer
authors.forename: F M
authors.initials: FM
authors.lastname: Bareyre
authors.forename: V M
authors.initials: VM
authors.lastname: Lee
authors.forename: J Q
authors.initials: JQ
authors.lastname: Trojanowski
authors.forename: L
authors.initials: L
authors.lastname: Longhi
authors.forename: R
authors.initials: R
authors.lastname: Hoover
authors.forename: K E
authors.initials: KE
authors.lastname: Saatman
authors.forename: R
authors.initials: R
authors.lastname: Raghupathi
authors.forename: S
authors.initials: S
authors.lastname: Hoshino
authors.forename: M S
authors.initials: MS
authors.lastname: Grady
authors.forename: T K
authors.initials: TK
authors.lastname: McIntosh
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology / Q000503:physiopathology*; D001924:Brain Concussion / Q000209:etiology*; D002319:Cardiovascular System / Q000503:physiopathology; D003071:Cognition; D006259:Craniocerebral Trauma / Q000150:complications* / Q000473:pathology / Q000503:physiopathology* / Q000523:psychology; D004198:Disease Susceptibility; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009069:Movement Disorders / Q000209:etiology; D012008:Recurrence; D012720:Severity of Illness Index