Blast Overpressure in Rats: Recreating a Battlefield Injury in the Laboratory

Abstract

Blast injury to the brain is the predominant cause of neurotrauma in current military conflicts, and its etiology is largely undefined. Using a compression-driven shock tube to simulate blast effects, we assessed the physiological, neuropathological, and neurobehavioral consequences of airblast exposure, and also evaluated the effect of a Kevlar protective vest on acute mortality in rats and on the occurrence of traumatic brain injury (TBI) in those that survived. This approach provides survivable blast conditions under which TBI can be studied. Striking neuropathological changes were caused by both 126- and 147-kPa airblast exposures. The Kevlar vest, which encased the thorax and part of the abdomen, greatly reduced airblast mortality, and also ameliorated the widespread fiber degeneration that was prominent in brains of rats not protected by a vest during exposure to a 126-kPa airblast. This finding points to a significant contribution of the systemic effects of airblast to its brain injury pathophysiology. Airblast of this intensity also disrupted neurologic and neurobehavioral performance (e.g., beam walking and spatial navigation acquisition in the Morris water maze). When immediately followed by hemorrhagic hypotension, with MAP maintained at 30 mm Hg, airblast disrupted cardiocompensatory resilience, as reflected by reduced peak shed blood volume, time to peak shed blood volume, and time to death. These findings demonstrate that shock tube-generated airblast can cause TBI in rats, in part through systemic mediation, and that the resulting brain injury significantly impacts acute cardiovascular homeostatic mechanisms as well as neurobehavioral function.

Preliminary studies on differential expression of auditory functional genes in the brain after repeated blast exposures

“…Groups of isoflurane (4%) anesthetized animals (n = 6 for sham and n = 6 for blast) were exposed to repeated blast exposures (20.6 psi), as reported previously, using a shock tube [9,36,[38][39]. At a 6 h time point after the last blast exposure, three animals each from sham and blast groups were euthanized, and the brain tissue was collected after necropsy and separated into various regions as described earlier [39].…”

“…Auditory/vestibular injuries from blast traumatic brain injury (TBI) can cause increased incidence of tinnitus and hearing loss, which worsens over time if not treated [1][2][3][4]. Shock waves generated from explosive blasts are reported to be destructive to both gas-and fluid-filled structures of the body, including the lungs, intestines, brain, eyes, nose, and middle ear [5][6][7][8][9]. Blast-induced damage to the auditory system can be the consequence of either direct exposure of the auditory canal to blast shock waves or TBI and impairment in the central auditory processing involving different brain regions after blast exposure.…”

Animal models for the study of military-related, blast-induced traumatic brain injury

“…Perhaps the most widely employed version is the shock tube utilized by researchers at the Walter Reed Institute for Army Research/Naval Medical Research Center [27][28][29][30]. A 30 cm diameter, 5.33 m long galvanized steel tube is attached to a smaller pipe of the same diameter.…”

“…Intracranial measures in anesthetized rats demonstrated overpressure within the cerebral ventricles in the range of 30-40 kPa [31], and that blast effects upon intracranial pressure persisted for hours after exposure [24]. Long [28] reports that shock tube exposure at relatively higher levels (126-147 kPa) leads to cerebral hemorrhage, necrosis, cortical cell loss, gliosis, and widespread fiber degeneration, which is not reported in many studies with fluid percussion or control cortical impact injury; others also have reported little evidence of obvious focal cortical injury [25,31]. Compared to the methods described in A-C, the shock tube permits whole-body exposure, which is relevant to body effects from blast on neurological function, and studies related to the impact of armor or protective clothing are feasible [25,28].…”

“…Long [28] reports that shock tube exposure at relatively higher levels (126-147 kPa) leads to cerebral hemorrhage, necrosis, cortical cell loss, gliosis, and widespread fiber degeneration, which is not reported in many studies with fluid percussion or control cortical impact injury; others also have reported little evidence of obvious focal cortical injury [25,31]. Compared to the methods described in A-C, the shock tube permits whole-body exposure, which is relevant to body effects from blast on neurological function, and studies related to the impact of armor or protective clothing are feasible [25,28]. Finally, an obvious feature of the shock tube is that rodents sustain a closed head injury, and one can relate neuropathological and behavioral changes to physical characteristics such as peak pressure amplitude and exposure duration.…”