Stress and Traumatic Brain Injury: A Behavioral, Proteomics, and Histological Study

Abstract

Psychological stress and traumatic brain injury (TBI) can both result in lasting neurobehavioral abnormalities. Post-traumatic stress disorder and blast induced TBI (bTBI) have become the most significant health issues in current military conflicts. Importantly, military bTBI virtually never occurs without stress. In this experiment, we assessed anxiety and spatial memory of rats at different time points after repeated exposure to stress alone or in combination with a single mild blast. At 2 months after injury or sham we analyzed the serum, prefrontal cortex (PFC), and hippocampus (HC) of all animals by proteomics and immunohistochemistry. Stressed sham animals showed an early increase in anxiety but no memory impairment at any measured time point. They had elevated levels of serum corticosterone (CORT) and hippocampal IL-6 but no other cellular or protein changes. Stressed injured animals had increased anxiety that returned to normal at 2 months and significant spatial memory impairment that lasted up to 2 months. They had elevated serum levels of CORT, CK-BB, NF-H, NSE, GFAP, and VEGF. Moreover, all of the measured protein markers were elevated in the HC and the PFC; rats had an increased number of TUNEL-positive cells in the HC and elevated GFAP and Iba1 immunoreactivity in the HC and the PFC. Our findings suggest that exposure to repeated stress alone causes a transient increase in anxiety and no significant memory impairment or cellular and molecular changes. In contrast, repeated stress and blast results in lasting behavioral, molecular, and cellular abnormalities characterized by memory impairment, neuronal and glial cell loss, inflammation, and gliosis. These findings may have implications in the development of diagnostic and therapeutic measures for conditions caused by stress or a combination of stress and bTBI.

Blast Exposure Induces Post-Traumatic Stress Disorder-Related Traits in a Rat Model of Mild Traumatic Brain Injury

“…33 These studies have documented a variety of, at least, short-term effects, suggesting that blast can be associated with anxiety as well as impairments in a variety of learning and memory tasks. 5,26,31,34,36,43,47,49,50 One study also reported impairments in prepulse inhibition immediately after blast exposure, changes that had mostly recovered by 90 days after exposure. 38 We utilized a rat model of mTBI in which adult male rats were exposed to a controlled blast overpressure injury in a shock tube.…”

“…23 Animals have been exposed to various forms of blast ranging from direct exposure to live explosives to controlled blast waves produced by compressed-air generators (reviewed in Elder et al 1 ) with activity in this area increasing dramatically in rodent models in recent years. 5, A number of studies have begun to look at the behavioral effects of blast across a range of blast exposures 5,26,31,33,34,36,38,43,[47][48][49][50] using blast alone or blast in combination with repeated stress 36 or other factors such as transportation or anesthesia. 33 These studies have documented a variety of, at least, short-term effects, suggesting that blast can be associated with anxiety as well as impairments in a variety of learning and memory tasks.…”

Improving aeration for efficient oxygenation in sea bass sea cages. Blood, brain and gill histology

“…We maintained the air pressure in the water at 4 bar in order to have the least amount of water turbulence and to decrease the chance of exposing the fish to this stress factor. In mammals, stress resulted in a transient increase in anxiety, with no detectable brain tissue damage [54]. Hypoxia can lead to brain damage.…”

The role of biomarkers and MEG-based imaging markers in the diagnosis of post-traumatic stress disorder and blast-induced mild traumatic brain injury

“…In humans, the observation that repeated mild injuries could result in chronic traumatic encephalopathy (CTE) (Lakis et al, 2013;Stein et al, 2014). has influenced scientists to start experimental projects on repeated mild blast induced TBI (Petraglia et al, 2014a,b;Glushakova et al, 2014;Goldstein et al, 2014).…”

“…blast models that make use of rodents and pigs. Refined behavioral tests with a high sensitivity for stress reactions similar to posttraumatic stress will be important in the future work with blast Kovesdi et al, 2011;Kwon et al, 2011). Additional experiments are required to enable an understanding of the co-morbidity of TBI and PTSD.…”