Interaction of Traumatic Brain Injury & Posttraumatic Stress Disorder: A Neurobehavioral & Inflammation Based Animal Study

Abstract

Comorbidity of post-traumatic stress disorder (PTSD) with traumatic brain injury (TBI) produces a syndrome more severe than PTSD or TBI alone [2] [3] . Both PTSD and TBI produce a long-lasting neuroinflammation, which potentially contributes to their chronic affective and cognitive deficits. This thesis studies the potential interactions of animal models of TBI and PTSD in C57BL/6 mice using neurobehavioral assays and immunohistological analysis focused on neuroinflammation. The first aim of the study investigated cognitive deficits arising from experimental TBI, PTSD or co-morbid TBI-PTSD models using Barnes Maze and Active Place Avoidance tasks. The second aim of the study assessed the affective deficits in the TBI, PTSD and co-morbid TBI-PTSD models using Elevated Plus Maze and Acoustic Startle Response tasks. Five groups of mice received either: 1) Sham-treatment 2) closed head injury (CHI), a model for TBI 3) chronic variable stress (CVS), a model for PTSD, or two models of combined TBI & PTSD that differed in the order of the insults, 4) CHI -> CVS, 5) CVS -> CHI. A major finding was that CVS -> CHI group had significantly larger cognitive deficits based on increased latency to find target box on Barnes Maze, deficit in acquiring the area of shock zone in the APA task. The CVS ->CHI group also had significantly larger affective deficit as measured by higher percent freezing episodes while performing the 90dB intensity ASR trials, and lack of habituation response in the 120dB burst trials. The cognitive and affective deficits of CVSCHI group was accompanied by increased hippocampal inflammation as measured by Iba-1, Arginase-1 and TSPO level. This increased inflammation correlated strongly with the extent of the behavioral deficits. These results support a central role of neuroinflammation in inducing neurobehavioral deficits in combined models of TBI and PTSD. Most importantly, the selective deficits of the CVS ->CHI group, highlights the sequential importance in acquiring TBI and PTSD.