Post-Traumatic Stress Disorder Delineating the Progression and Underlying Mechanisms Following Blast Traumatic Brain Injury.
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ABSTRACT:
SUBMITTER: Wold BL
PROVIDER: S-EPMC5993449 | biostudies-literature | 2018
REPOSITORIES: biostudies-literature
Publications
Post-Traumatic Stress Disorder Delineating the Progression and Underlying Mechanisms Following Blast Traumatic Brain Injury.
Lucke-Wold Brandon B Nolan Richard R Nwafor Divine D Nguyen Linda L Cheyuo Cletus C Turner Ryan R Rosen Charles C Marsh Robert R
Journal of neuroscience and neuropharmacology 20180302 1
Posttraumatic Stress Disorder (PTSD) is a devastating condition that can develop after blast Traumatic Brain Injury (TBI). Ongoing work has been performed to understand how PTSD develops after injury. In this review, we highlight how PTSD affects individuals, discuss what is known about the physiologic changes to the hypothalamic pituitary axis and neurotransmitter pathways, and present an overview of genetic components that may predispose individuals to developing PTSD. We then provide an overv ...[more]
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Project description:Traumatic brain injury (TBI) is associated with increased risk for mental health disorders, impacting post-injury quality of life and societal reintegration. TBI is also associated with deficits in psychosocial processing, defined as the cognitive integration of social and emotional behaviors, however little is known about how these deficits manifest and their contributions to post-TBI mental health. In this pre-clinical investigation using rats, a single mild blast TBI (mbTBI) induced impairment of psychosocial processing in the absence of confounding physical polytrauma, post-injury motor deficits, affective abnormalities, or deficits in non-social behavior. Impairment severity correlated with acute upregulations of a known oxidative stress metabolite, 3-hydroxypropylmercapturic acid (3-HPMA), in urine. Resting state fMRI alterations in the acute post-injury period implicated key brain regions known to regulate psychosocial behavior, including orbitofrontal cortex (OFC), which is congruent with our previous report of elevated acrolein, a marker of neurotrauma and 3-HPMA precursor, in this region following mbTBI. OFC of mbTBI-exposed rats demonstrated elevated mRNA expression of metabotropic glutamate receptors 1 and 5 (mGluR1/5) and injection of mGluR1/5-selective agonist in OFC of uninjured rats approximated mbTBI-induced psychosocial processing impairment, demonstrating a novel role for OFC in this psychosocial behavior. Furthermore, OFC may serve as a hotspot for TBI-induced disruption of psychosocial processing and subsequent mental health disorders.
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Project description:Disasters are traumatic events that may result in a wide range of mental and physical health consequences. Post-traumatic stress disorder (PTSD) is probably the most commonly studied post-disaster psychiatric disorder. This review aimed to systematically assess the evidence about PTSD following exposure to disasters. MethodA systematic search was performed. Eligible studies for this review included reports based on the DSM criteria of PTSD symptoms. The time-frame for inclusion of reports in this review is from 1980 (when PTSD was first introduced in DSM-III) and February 2007 when the literature search for this examination was terminated.We identified 284 reports of PTSD following disasters published in peer-reviewed journals since 1980. We categorized them according to the following classification: (1) human-made disasters (n=90), (2) technological disasters (n=65), and (3) natural disasters (n=116). Since some studies reported on findings from mixed samples (e.g. survivors of flooding and chemical contamination) we grouped these studies together (n=13).The body of research conducted after disasters in the past three decades suggests that the burden of PTSD among persons exposed to disasters is substantial. Post-disaster PTSD is associated with a range of correlates including sociodemographic and background factors, event exposure characteristics, social support factors and personality traits. Relatively few studies have employed longitudinal assessments enabling documentation of the course of PTSD. Methodological limitations and future directions for research in this field are discussed.
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Project description:Recent wars in Iraq and Afghanistan have accounted for an estimated 270,000 blast exposures among military personnel. Blast traumatic brain injury (TBI) is the 'signature injury' of modern warfare. Blood brain barrier (BBB) disruption following blast TBI can lead to long-term and diffuse neuroinflammation. In this study, we investigate for the first time the role of bryostatin-1, a specific protein kinase C (PKC) modulator, in ameliorating BBB breakdown. Thirty seven Sprague-Dawley rats were used for this study. We utilized a clinically relevant and validated blast model to expose animals to moderate blast exposure. Groups included: control, single blast exposure, and single blast exposure + bryostatin-1. Bryostatin-1 was administered i.p. 2.5 mg/kg after blast exposure. Evan's blue, immunohistochemistry, and western blot analysis were performed to assess injury. Evan's blue binds to albumin and is a marker for BBB disruption. The single blast exposure caused an increase in permeability compared to control (t?=?4.808, p?<?0.05), and a reduction back toward control levels when bryostatin-1 was administered (t?=?5.113, p?<?0.01). Three important PKC isozymes, PKC?, PKC?, and PKC?, were co-localized primarily with endothelial cells but not astrocytes. Bryostatin-1 administration reduced toxic PKC? levels back toward control levels (t?=?4.559, p?<?0.01) and increased the neuroprotective isozyme PKC? (t?=?6.102, p?<?0.01). Bryostatin-1 caused a significant increase in the tight junction proteins VE-cadherin, ZO-1, and occludin through modulation of PKC activity. Bryostatin-1 ultimately decreased BBB breakdown potentially due to modulation of PKC isozymes. Future work will examine the role of bryostatin-1 in preventing chronic neurodegeneration following repetitive neurotrauma.
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