Citation

Dapul H, Park J, Zhang J, Lee C, Daneshmand A, Lok J, Ayata C, Gray T, Scalzo A, Qiu J, Lo EH, Whalen M. J. Neurotrauma 2013; 30(5): 382-391.

Affiliation

MGH, Pediatrics, Boston, Massachusetts, United States; hdapul@maimonidesmed.org.

Copyright

(Copyright © 2013, Mary Ann Liebert Publishers)

DOI

10.1089/neu.2012.2536

PMID

23153355

Abstract

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. Here 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/s) and a closed head injury (CHI) model at one of two levels of injury (53 vs. 83 g weight drop from 66 in). Compared to 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 postinjury 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 TBI patients, and may prove useful for testing putative therapies.

Language: en