The importance of systemic response in the pathobiology of blast-induced neurotrauma

Abstract

Due to complex injurious environment where multiple blast effects interact with the body parallel, blast-induced neurotrauma is a unique clinical entity induced by systemic, local, and cerebral responses. Activation of autonomous nervous system; sudden pressure increase in vital organs such as lungs and liver; and activation of neuroendocrine–immune system are among the most important mechanisms that contribute significantly to molecular changes and cascading injury mechanisms in the brain. It has been hypothesized that vagally mediated cerebral effects play a vital role in the early response to blast: this assumption has been supported by experiments where bilateral vagotomy mitigated bradycardia, hypotension, and apnea, and also prevented excessive metabolic alterations in the brain of animals exposed to blast. Clinical experience suggests specific blast–body–nervous system interactions such as (1) direct interaction with the head either through direct passage of the blast wave through the skull or by causing acceleration and/or rotation of the head; and (2) via hydraulic interaction, when the blast overpressure compresses the abdomen and chest, and transfers its kinetic energy to the body's fluid phase, initiating oscillating waves that traverse the body and reach the brain. Accumulating evidence suggests that inflammation plays important role in the pathogenesis of long-term neurological deficits due to blast. These include memory decline, motor function and balance impairments, and behavioral alterations, among others. Experiments using rigid body- or head protection in animals subjected to blast showed that head protection failed to prevent inflammation in the brain or reduce neurological deficits, whereas body protection was successful in alleviating the blast-induced functional and morphological impairments in the brain.

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

“…All methods that could facilitate a good translation to clinical data (serological biomarkers, neurophysiolgy and imaging) are recommended. Dr. Ibolja Cernak has shown that blast TBI can be a systemic reaction to blast (Cernak, 2010). General inflammatory reactions from the primary blast can contribute to the reactions of the brain.…”

“…The propagation of pressure waves through the body in blast trauma is still a subject of disagreement. Important data can be retrieved by carefully planned experiments utilizing incomplete body protection (Cernak, 2010). The importance of repeated mild TBI for development of late development of neurodegenerative disease has been documented in sports medicine (Guskiewicz et al, 2005) and repeated injuries will undoubtedly be included in a number of protocols for research on blast TBI.…”

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

“…The surge in catecholamine levels in the brain also may have a relation to inflammation. 64 It has been shown by Cernak 65 that there is a systemic inflammatory response to blast and that this includes the brain. Interestingly, no effects on monoamine transmitter levels were seen in the PFC, in spite of the fact that PFC is a key region in cognition and emotions.…”

Screening of Biochemical and Molecular Mechanisms of Secondary Injury and Repair in the Brain after Experimental Blast-Induced Traumatic Brain Injury in Rats

“…[13][14][15] An approach to screen mechanisms in a blast TBI model at the threshold of detectible neuropathology could provide useful insight into therapeutic targets. Clues as to possible secondary injury mechanisms after experimental blast TBI were first provided by Cernak and colleagues, 10 who reported on a role for oxidative stress (OS) and neuroinflammation, 16 but studies are limited.…”