Mild head injury increasing the brain's vulnerability to a second concussive impact

作者：Helmut L. Laurer, Florence M. Bareyre, Virginia M. Y. C. Lee, John Q. Trojanowski, Luca Giovanni Longhi, Rachel C. Hoover, Kathryn E. Saatman, Ramesh Raghupathi, Shigeru Hoshino, Michael Sean Grady, Tracy K. McIntosh · 发表于：Journal of neurosurgery · 年份：2001 · DOI：10.3171/jns.2001.95.5.0859 · 被引用次数：321 · 研究领域：Traumatic Brain Injury Research、Traumatic Brain Injury and Neurovascular Disturbances、Automotive and Human Injury Biomechanics

OBJECT: 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...