Gait and Conditioned Fear Impairments in a Mouse Model of Comorbid TBI and PTSD.

Natasha Avalon Gardner,Mara E. Kaiser,Carolyn E. Jones,Peyton Teutsch,Miranda M. Lim

doi:10.1155/2018/6037015

Abstract

Study Objectives Traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) commonly cooccur. Approaches to research and treatment of these disorders have been segregated, despite overlapping symptomology. We and others have hypothesized that comorbid TBI + PTSD generates worse symptoms than either condition alone. We present a mouse model of comorbid TBI + PTSD to further explore this condition. Methods A mouse model of TBI + PTSD was generated using the single prolonged stress (SPS) protocol in combination with the controlled cortical impact (CCI) protocol. This resulted in four experimental groups: control, TBI, PTSD, and TBI + PTSD. Behavioral phenotyping included gait analysis, contextual fear conditioning, acoustic startle response, and prepulse inhibition. Results Mice in the TBI + PTSD group showed a significantly impaired gait compared to their counterparts with TBI alone as well as control mice. Mice in the TBI + PTSD group showed significantly impaired contextual fear recall compared to controls. Prepulse inhibition testing revealed intact acoustic startle and auditory sensory gating. Conclusions These results indicate that SPS paired with CCI in mice produces unique behavioral impairments in gait and fear recall that are not present in either condition alone. Further studies are underway to examine additional behavioral, physiological, and pathological phenotypes in this combined model of TBI + PTSD.

Highlights

Traumatic brain injury (TBI) is a change in neural functioning caused by an external force to the head, resulting in mild to severe injury [1]
Paw placement positioning was altered in the left side (Kruskal-Wallis, p = 0 028), with differences emerging between the TBI + Posttraumatic stress disorder (PTSD) group and the TBI group (p = 0 018) (Figure 2(c))
In this model of TBI + PTSD, we found that stance width in the forelimbs was dramatically decreased and paw placement position, a measure that indicates the amount of ipsilateral overlap between fore and hind paws, was preferentially increased on the left side in the TBI + PTSD mice

Summary

Introduction

Traumatic brain injury (TBI) is a change in neural functioning caused by an external force to the head, resulting in mild to severe injury [1]. TBI results in persistent symptoms including changes in cognition (e.g., difficulty concentrating or remembering), problems with balance, and increased anxiety. Posttraumatic stress disorder (PTSD) can develop after a traumatizing event and frequently results in behavioral changes that overlap in symptomatology with TBI, including cognitive dysfunction, heightened anxiety, and exaggerated startle response [4]. Compared to the average population, rates and symptom severity of PTSD are reported to be significantly higher in Veterans [5]. Both TBI and PTSD are associated with lower quality of life and increased risk for psychological and medical disorders compared to healthy individuals [6]. Veterans with TBI in particular are at a higher risk for developing PTSD [6]

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