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Original Research ARTICLE

Front. Behav. Neurosci., 23 June 2014 | http://dx.doi.org/10.3389/fnbeh.2014.00213

Neurobehavioral, neuropathological and biochemical profiles in a novel mouse model of co-morbid post-traumatic stress disorder and mild traumatic brain injury

Joseph O. Ojo1*, M. Banks Greenberg1, Paige Leary1, Benoit Mouzon1,2,3, Corbin Bachmeier1,2,3, Michael Mullan1,2,3, David M. Diamond2,4 and Fiona Crawford1,2,3
  • 1Roskamp Institute, Sarasota, FL, USA
  • 2Research and Development Service, James A. Haley Veterans' Hospital, Tampa, FL, USA
  • 3Department of Life sciences, The Open University, Milton Keynes, UK
  • 4Department of Psychology, Department of Molecular Pharmacology and Physiology, Center for Preclinical and Clinical Research on PTSD, University of South Florida, Tampa, FL, USA

Co-morbid mild traumatic brain injury (mTBI) and post-traumatic stress disorder (PTSD) has become the signature disorder for returning combat veterans. The clinical heterogeneity and overlapping symptomatology of mTBI and PTSD underscore the need to develop a preclinical model that will enable the characterization of unique and overlapping features and allow discrimination between both disorders. This study details the development and implementation of a novel experimental paradigm for PTSD and combined PTSD-mTBI. The PTSD paradigm involved exposure to a danger-related predator odor under repeated restraint over a 21 day period and a physical trauma (inescapable footshock). We administered this paradigm alone, or in combination with a previously established mTBI model. We report outcomes of behavioral, pathological and biochemical profiles at an acute timepoint. PTSD animals demonstrated recall of traumatic memories, anxiety and an impaired social behavior. In both mTBI and combination groups there was a pattern of disinhibitory like behavior. mTBI abrogated both contextual fear and impairments in social behavior seen in PTSD animals. No major impairment in spatial memory was observed in any group. Examination of neuroendocrine and neuroimmune responses in plasma revealed a trend toward increase in corticosterone in PTSD and combination groups, and an apparent increase in Th1 and Th17 proinflammatory cytokine(s) in the PTSD only and mTBI only groups respectively. In the brain there were no gross neuropathological changes in any groups. We observed that mTBI on a background of repeated trauma exposure resulted in an augmentation of axonal injury and inflammatory markers, neurofilament L and ICAM-1 respectively. Our observations thus far suggest that this novel stress-trauma-related paradigm may be a useful model for investigating further the overlapping and distinct spatio-temporal and behavioral/biochemical relationship between mTBI and PTSD experienced by combat veterans.

Keywords: post-traumatic stress disorder, mild traumatic brain injury, mouse models, anxiety and social behavior, cognitive function, plasma and brain biomarkers

Citation: Ojo JO, Greenberg MB, Leary P, Mouzon B, Bachmeier C, Mullan M, Diamond DM and Crawford F (2014) Neurobehavioral, neuropathological and biochemical profiles in a novel mouse model of co-morbid post-traumatic stress disorder and mild traumatic brain injury. Front. Behav. Neurosci. 8:213. doi: 10.3389/fnbeh.2014.00213

Received: 08 February 2014; Accepted: 26 May 2014;
Published online: 23 June 2014.

Edited by:

James P. Herman, University of Cincinnati, USA

Reviewed by:

Seth Davin Norrholm, Emory University School of Medicine, USA
Renu Sah, University of Cincinnati, USA

Copyright © 2014 Ojo, Greenberg, Leary, Mouzon, Bachmeier, Mullan, Diamond and Crawford. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Joseph O. Ojo, Roskamp Institute, 2040 Whitfield Avenue, Sarasota, FL 343243, USA e-mail: bojo@roskampinstitute.net