• Journal of neurotrauma · Mar 2013

    Concussive injury before or after controlled cortical impact exacerbates histopathology and functional outcome in a mixed traumatic brain injury model in mice.

    • Cenk Ayata, Eng H Lo, Michael J Whalen, Heda R Dapul, Ali DanEshmand, Josephine Lok, Tory Gray, and Allison Scalzo.
    • Neuroscience Center , Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.
    • J. Neurotrauma. 2013 Mar 1;30(5):382-91.

    AbstractTraumatic brain injury (TBI) may involve diverse injury mechanisms (e.g., focal impact vs. diffuse impact loading). Putative therapies developed in TBI models featuring a single injury mechanism may fail in clinical trials if the model does not fully replicate multiple injury subtypes, which may occur concomitantly in a given patient. We report development and characterization of a mixed contusion/concussion TBI model in mice using controlled cortical impact (CCI; 0.6 mm depth, 6 m/sec) and a closed head injury (CHI) model at one of two levels of injury (53 vs. 83 g weight drop from 66 in). Compared with CCI or CHI alone, sequential CCI-CHI produced additive effects on loss of consciousness (p<0.001), acute cell death (p<0.05), and 12-day lesion size (p<0.05) but not brain edema or 48-h contusion volume. Additive effects of CHI and CCI on post-injury motor (p<0.05) and cognitive (p<0.005) impairment were observed with sequential CCI-CHI (83 g). The data suggest that concussive forces, which in isolation do not induce histopathological damage, exacerbate histopathology and functional outcome after cerebral contusion. Sequential CHI-CCI may model complex injury mechanisms that occur in some patients with TBI and may prove useful for testing putative therapies.

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