Cellular Mechanisms and Behavioral Outcomes in Blast-Induced Neurotrauma: Comparing Experimental Setups.
Blast-induced neurotrauma (BINT) has increased in incidence over the past decades and can result in cognitive issues that have debilitating consequences. The exact primary and secondary mechanisms of injury have not been elucidated and appearance of cellular injury can vary based on many factors, such as blast overpressure magnitude and duration. Many methodologies to study blast neurotrauma have been employed, ranging from open-field explosives to experimental shock tubes for producing free-field blast waves. While there are benefits to the various methods, certain specifications need to be accounted for in order to properly examine BINT. Primary cell injury mechanisms, occurring as a direct result of the blast wave, have been identified in several studies and include cerebral vascular damage, blood-brain barrier disruption, axonal injury, and cytoskeletal damage. Secondary cell injury mechanisms, triggered subsequent to the initial insult, result in the activation of several molecular cascades and can include, but are not limited to, neuroinflammation and oxidative stress. The collective result of these secondary injuries can lead to functional deficits. Behavioral measures examining motor function, anxiety traits, and cognition/memory problems have been utilized to determine the level of injury severity. While cellular injury mechanisms have been identified following blast exposure, the various experimental models present both concurrent and conflicting results. Furthermore, the temporal response and progression of pathology after blast exposure have yet to be detailed and remain unclear due to limited resemblance of methodologies. This chapter summarizes the current state of blast neuropathology and emphasizes the need for a standardized preclinical model of blast neurotrauma.
School of Biomedical Engineering and Sciences, Virginia Tech, 447 Kelly Hall, 325 Stanger Street, Blacksburg, VA, 24061, USA.
Zachary S
ZS
Bailey
School of Biomedical Engineering and Sciences, Virginia Tech, 447 Kelly Hall, 325 Stanger Street, Blacksburg, VA, 24061, USA.
W Brad
WB
Hubbard
School of Biomedical Engineering and Sciences, Virginia Tech, 447 Kelly Hall, 325 Stanger Street, Blacksburg, VA, 24061, USA. pvord@vt.edu.
Pamela J
PJ
VandeVord
D000818:Animals; D001369:Axons / Q000378:metabolism / Q000473:pathology; D001522:Behavior, Animal; D001753:Blast Injuries / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D001812:Blood-Brain Barrier / Q000378:metabolism; D002560:Cerebrovascular Circulation; D003599:Cytoskeleton; D004195:Disease Models, Animal; D007249:Inflammation; D008297:Male; D018384:Oxidative Stress; D051381:Rats; D020196:Trauma, Nervous System / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology
Blast; In vivo; Methodology; Neuropathology; Neurotrauma; Preclinical models; Shock tube; Shock wave; Traumatic brain injury