Vascular and inflammatory factors in the pathophysiology of blast-induced brain injury.

Gregory A Elder,Patrick R Hof,Miguel A Gama Sosa,James Radford Stone,Dara L Dickstein,Rita De Gasperi,Fatemeh Haghighi,Stephen T Ahlers

doi:10.3389/fneur.2015.00048

Abstract

Blast-related traumatic brain injury (TBI) has received much recent attention because of its frequency in the conflicts in Iraq and Afghanistan. This renewed interest has led to a rapid expansion of clinical and animal studies related to blast. In humans, high-level blast exposure is associated with a prominent hemorrhagic component. In animal models, blast exerts a variety of effects on the nervous system including vascular and inflammatory effects that can be seen with even low-level blast exposures which produce minimal or no neuronal pathology. Acutely, blast exposure in animals causes prominent vasospasm and decreased cerebral blood flow along with blood-brain barrier breakdown and increased vascular permeability. Besides direct effects on the central nervous system, evidence supports a role for a thoracically mediated effect of blast; whereby, pressure waves transmitted through the systemic circulation damage the brain. Chronically, a vascular pathology has been observed that is associated with alterations of the vascular extracellular matrix. Sustained microglial and astroglial reactions occur after blast exposure. Markers of a central and peripheral inflammatory response are found for sustained periods after blast injury and include elevation of inflammatory cytokines and other inflammatory mediators. At low levels of blast exposure, a microvascular pathology has been observed in the presence of an otherwise normal brain parenchyma, suggesting that the vasculature may be selectively vulnerable to blast injury. Chronic immune activation in brain following vascular injury may lead to neurobehavioral changes in the absence of direct neuronal pathology. Strategies aimed at preventing or reversing vascular damage or modulating the immune response may improve the chronic neuropsychiatric symptoms associated with blast-related TBI.

Highlights

It was first recognized during world war (WW) I that blast exposure can be associated with psychological and neurological symptoms reminiscent of both the post-concussion syndrome and what would be called post-traumatic stress disorder (PTSD) [1]
Estimates are that 10–20% of veterans returning from these conflicts have suffered a traumatic brain injury (TBI) with the most frequent cause being blast exposure related to improvised explosive devices (IED) [8, 9]
What became apparent was that many Iraq and Afghanistan veterans were presenting to veterans affairs (VA) hospitals and other facilities with symptoms suggestive of the residual effects of mild TBIs that were never recognized prior to discharge

Summary

Introduction

It was first recognized during world war (WW) I that blast exposure can be associated with psychological and neurological symptoms reminiscent of both the post-concussion syndrome and what would be called post-traumatic stress disorder (PTSD) [1]. 7 days post-injury activation of microglia in hippocampus of 69 kPa group, increased GFAP-positive astrocytes in hippocampus of 97 and 165 kPa groups returned to normal by 72 h, Kuehn et al [34] observed abnormal vascular immunolabeling for IgG in cerebellum, thalamus, and entorhinal cortex for as long as 7 days after blast exposure in rats.

Results

Conclusion