Neurotransmitter Systems in a Mild Blast Traumatic Brain Injury Model: Catecholamines and Serotonin

Abstract

Exposure to improvised explosive devices can result in a unique form of traumatic brain injury-blast-induced traumatic brain injury (bTBI). At the mild end of the spectrum (mild bTBI [mbTBI]), there are cognitive and mood disturbances. Similar symptoms have been observed in post-traumatic stress disorder caused by exposure to extreme psychological stress without physical injury. A role of the monoaminergic system in mood regulation and stress is well established but its involvement in mbTBI is not well understood. To address this gap, we used a rodent model of mbTBI and detected a decrease in immobility behavior in the forced swim test at 1 d post-exposure, coupled with an increase in climbing behavior, but not after 14 d or later, possibly indicating a transient increase in anxiety-like behavior. Using in situ hybridization, we found elevated messenger ribonucleic acid levels of both tyrosine hydroxylase and tryptophan hydroxylase 2 in the locus coeruleus and the dorsal raphe nucleus, respectively, as early as 2 h post-exposure. High-performance liquid chromatography analysis 1 d post-exposure primarily showed elevated noradrenaline levels in several forebrain regions. Taken together, we report that exposure to mild blast results in transient changes in both anxiety-like behavior and brain region-specific molecular changes, implicating the monoaminergic system in the pathobiology of mbTBI.

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

“…Such experiments could be combined with biomarker sampling, behavior analysis such as the Forced Swim Test and functional imaging. A recent study has revealed significant changes in catecholamines and serotonin in rodents exposed to a mild TBI (Kawa et al, 2014).…”

“…Such experiments could be combined with biomarker sampling, behavior analysis such as the Forced Swim Test and functional imaging. A recent study has revealed significant changes in catecholamines and serotonin in rodents exposed to a mild TBI (Kawa et al, 2014).One way to accomplish a better translation between animal experiments and the clinic would be to employ the same methodology for analysis. Imaging, e.g.…”

Upregulation of Interferon Regulatory Factor 6 Promotes Neuronal Apoptosis After Traumatic Brain Injury in Adult Rats

“…Traumatic brain injury (TBI) causes serious adverse outcomes including death and disability in both industrialized countries (Coronado et al 2011) and developing countries (Kawa et al 2014;Sarkar et al 2014). Two phases of TBI have been identified: primary injury and an ensuing secondary reaction.…”

Differential expression of microRNAs in the brains of mice subjected to increasing grade of mild traumatic brain injury

“…It has also been reported earlier that miRNAs may play a role in PTSD pathophysiology [47]. A recent study by Kawa et al [75] shows a correlation of increase in tryptophan hydroxylase 2, a rate-limiting enzyme for serotonin synthesis, with anxiety-like behaviour in the brain after mTBI. Similarly, this study has reported depression and emotional distress in the mice using the same mTBI model as previously used [13].…”