An introductory characterization of a combat-casualty-care relevant swine model of closed head injury resulting from exposure to explosive blast

Abstract

Explosive blast has been extensively used as a tactical weapon in Operation Iraqi Freedom (OIF) and more recently in Operation Enduring Freedom(OEF). The polytraumatic nature of blast injuries is evidence of their effectiveness,and brain injury is a frequent and debilitating form of this trauma. In-theater clinical observations of brain-injured casualties have shown that edema, intracranial hemorrhage, and vasospasm are the most salient pathophysiological characteristics of blast injury to the brain. Unfortunately, little is known about exactly how an explosion produces these sequelae as well as others that are less well documented. Consequently, the principal objective of the current report is to present a swine model of explosive blast injury to the brain. This model was developed during Phase I of the DARPA (Defense Advanced Research Projects Agency) PREVENT (Preventing Violent Explosive Neurotrauma) blast research program. A second objective is to present data that illustrate the capabilities of this model to study the proximal biomechanical causes and the resulting pathophysiological, biochemical,neuropathological, and neurological consequences of explosive blast injury to the swine brain. In the concluding section of this article, the advantages and limitations of the model are considered, explosive and air-overpressure models are compared, and the physical properties of an explosion are identified that potentially contributed to the in-theater closed head injuries resulting from explosions of improvised explosive devices (IEDs).

Blast-induced phenotypic switching in cerebral vasospasm

“…But, local ischemia resulting from acute vasospasms may play a significant role in the delayed onset of clinical manifestations of bTBI. The normal progression of cerebral vasospasm is an initial hypercontraction (26) followed by vessel remodeling (4-6) and narrowing (9). Here, we find that within 24 h of blastlike injury, mechanotransduction of extreme mechanical forces can induce both hypercontractility and phenotypic switching indicative of the onset of remodeling.…”

“…Traditionally cerebral vasospasm is attributed to subarachnoid hemorrhage (SAH), however, clinical reviews suggest that SAH is sufficient, but not necessary to potentiate cerebral vasospasm following bTBI (7). During blast injury, the cerebral vasculature likely bears significant acute pressure loads (8,9). The role of chronically elevated luminal pressures in potentiating arterial thickening and stiffening to reequilibrate wall stress is well established (10); however, the vascular response to rapid acute pressure increases is unknown.…”

A prospective, randomized Phase II clinical trial to evaluate the effect of combined hyperbaric and normobaric hyperoxia on cerebral metabolism, intracranial pressure, oxygen toxicity, and clinical outcome in severe traumatic brain injury

“…This study was a subsequent supplement to a larger prospective, randomized clinical trial. 45 This report differs from that previously published study in that O 2 delivery and cerebral metabolism were studied in the pericontusional areas of some patients and clinical outcome was assessed at 6 months using the GOS; moreover, in the present study, HBO 2 and NBH were evaluated in combination rather than separately.…”

“…The economic toll of TBI exceeds $60 billion per year. 18 Our previous investigations of HBO 2 Object. Preclinical and clinical investigations indicate that the positive effect of hyperbaric oxygen (HBO 2 ) for severe traumatic brain injury (TBI) occurs after rather than during treatment.…”

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.…”