期刊
JOURNAL OF NEUROTRAUMA
卷 30, 期 5, 页码 382-391出版社
MARY ANN LIEBERT, INC
DOI: 10.1089/neu.2012.2536
关键词
brain injury; cognition; concussion; controlled cortical impact; mice; models
资金
- [1R21NS075226]
- [RO1NS047447]
- [RO1NS064545]
Traumatic 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; 0.6mm 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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