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

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.

Increased Behavioral Deficits and Inflammation in a Mouse Model of Co-Morbid Traumatic Brain Injury and Post-Traumatic Stress Disorder

“…CHI inhibited the acoustic startle response with greater percentage of the mice freezing during trials of 110 dB ( Figure 2D). Three disparate experimental models of TBI; controlled cortical impact model, fluid percussion and weight drop showed a similar inhibition of acoustic startle response (Wolf et al, 2017;Teutsch et al, 2018;Bodnar et al, 2019). The underlying cause is unknown why head injury inhibits the acoustic startle response in multiple TBI models and is deserving of further study.…”

“…Acoustic startle frequently measures the Vmax of the startle response. Previous studies by others showed acoustic startle response was inhibited in a variety of different TBI models (Sackheim et al, 2017;Teutsch et al, 2018;Bodnar et al, 2019). Therefore, the frequency of trials that had a Vmax of zero was assessed.…”

Blast-Related Mild TBI Alters Anxiety-Like Behavior and Transcriptional Signatures in the Rat Amygdala

“…We also measured the acquisition of fear learning and both cued and contextual fear and found a trending effect of rBOP at chronic timepoint but no sub-acute effects. Some human studies (Glenn et al, 2017) and rodent models of the blast (Meyer et al, 2012;Davies et al, 2016) have found impaired fear acquisition following blast exposure, but there are still mixed findings of the effects of blast on cued and contextual fear recall (Elder et al, 2012;Meyer et al, 2012;Teutsch et al, 2018).…”

A Role for the Amygdala in Impairments of Affective Behaviors Following Mild Traumatic Brain Injury

“…Repetitive brain injury has been shown to lead to chronic deficits in social behavior, spatial working memory, spatial learning, and other prefrontal cortex and hippocampal-associated functions ( Cheng et al, 2014 ; Nolan et al, 2018 ). The worsening or development of affective behavioral deficits is frequently reported in preclinical models of single and repetitive TBI ( Teutsch et al, 2018 ; Popovitz et al, 2019 ; Beitchman et al, 2020 ), and mild TBI, and include spatial memory impairments, depression, anxiety, and impairments in fear-related behaviors, as seen in clinical populations ( Petraglia et al, 2014 ; Wright et al, 2017 ). Moreover, animals subjected to repetitive brain injuries are at an increased risk of experiencing prolonged behavioral impairments post-injury ( Petraglia et al, 2014 ).…”