Temporal Window of Vulnerability to Repetitive Experimental Concussive Brain Injury

作者：Luca Giovanni Longhi, Kathryn E. Saatman, Scott T. Fujimoto, Ramesh Raghupathi, David F. Meaney, Jason Davis, Asenia McMillan, Valeria Conte, Helmut L. Laurer, Sherman C. Stein, Nino Stocchetti, Tracy K. McIntosh · 发表于：Neurosurgery · 年份：2005 · DOI：10.1227/01.neu.0000149008.73513.44 · 被引用次数：312 · 研究领域：Traumatic Brain Injury Research、Traumatic Brain Injury and Neurovascular Disturbances、S100 Proteins and Annexins

OBJECTIVE: Repetitive concussive brain injury (CBI) is associated with cognitive alterations and increased risk of neurodegenerative disease. METHODS: To evaluate the temporal window during which the concussed brain remains vulnerable to a second concussion, anesthetized mice were subjected to either sham injury or single or repetitive CBI (either 3, 5, or 7 days apart) using a clinically relevant model of CBI. Cognitive, vestibular, and sensorimotor function (balance and coordination) were evaluated, and postmortem histological analyses were performed to detect neuronal degeneration, cytoskeletal proteolysis, and axonal injury. RESULTS: No cognitive deficits were observed in sham-injured animals or those concussed once. Mice subjected to a second concussion within 3 or 5 days exhibited significantly impaired cognitive function compared with either sham-injured animals (P < 0.05) or mice receiving a single concussion (P < 0.01). No cognitive deficits were observed when the interconcussion interval was extended to 7 days, suggestive of a transient vulnerability of the brain during the first 5 days after an initial concussion. Although all concussed mice showed transient motor deficits, vestibulomotor dysfunction was more pronounced in the group that sustained two concussions 3 days apart (P < 0.01 compared with all other groups). Although scattered degenerating neurons, evidence of cytoskeletal damage, and axonal injury were detected in selective brain regions between 72 hours...