Traumatic Brain Injury: An Overview of Pathobiology with Emphasis on Military Populations

Abstract

This review considers the pathobiology of non-impact blast-induced neurotrauma (BINT). The pathobiology of traumatic brain injury (TBI) has been historically studied in experimental models mimicking features seen in the civilian population. These brain injuries are characterized by primary damage to both gray and white matter and subsequent evolution of secondary pathogenic events at the cellular, biochemical, and molecular levels, which collectively mediate widespread neuro-degeneration. An emerging field of research addresses brain injuries related to the military, in particular blast-induced brain injuries. What is clear from the effort to date is that the pathobiology of military TBIs, particularly BINT, has characteristics not seen in other types of brain injury, despite similar secondary injury cascades. The pathobiology of primary BINT is extremely complex. It comprises systemic, local, and cerebral responses interacting and often occurring in parallel. Activation of the 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 significantly contributing to molecular changes and cascading injury mechanisms in the brain.

Modeling clinically relevant blast parameters based on scaling principles produces functional & histological deficits in rats

“…It remains unclear why specific brain regions may be more susceptible to blast-induced brain injury but one logical explanation is that of spallation. Spallation refers to the interface-based disruption that occurs between tissues of different densities upon a compression wave in the denser medium reflecting at the interface resulting in displacement and fragmentation of the denser medium into the less dense medium (Cernak and Noble-Haeusslein, 2010;Covey and Born, 2010;Yeh and Schecter, 2012). Spalling has been identified as a leading cause of endothelial injury and activation of microglia (Duckworth et al, 2012), consistent with our findings.…”

Antioxidant treatment reduces blast-induced cochlear damage and hearing loss

“…In conclusion, the blast model described herein meets the criteria described for good models by Cernak and Noble-Haeusslein (2010) for head trauma: 1) The mechanical force (blast) is controlled, reproducible and quantifiable; 2) The injuries as measured by ABR threshold shifts, DPOAE level shifts and cochlear hair cell loss are reproducible under controlled and quantifiable conditions; 3) The physical properties of the blast (amplitude and number of blast exposures) correlate with severity and nature of injury.…”

Impaired autophagy flux is associated with neuronal cell death after traumatic brain injury

“…18 Brain trauma initiates delayed progressive tissue damage through a cascade of molecular and cellular events leading to neuronal cell death. [18][19][20] The role of autophagy in this secondary neurodegeneration is uncertain. Increased markers of autophagy have been reported in the brain following TBI; [21][22][23][24] however, its cell-type specificity and the mechanism of induction remain unclear.…”