Modeling Primary Blast Injury in Isolated Spinal Cord White Matter

Abstract

Primary blast injury (PBI) is a common injury associated with present military conflicts and leads to significant neurological deficits. In order to prevent and treat this injury, an appropriate understanding of the biological response is required. A blast wave generator was created as an experimental model to elucidate this response by creating a repeatable blast injury on ex-vivo guinea pig spinal cord white matter. Subsequently, this study defines approximate limits for blast force and provides a relationship between axonal damage, nerve conduction parameters and functional recovery. Action potential generation and physical deficits of spinal cords exposed to blast injury were measured using a double sucrose gap-recording chamber and a dye-exclusion assay. Results express an inverse correlation between the severity of blast injury and degree of recovery. Such an approach is expected to contribute significantly to the detection and prediction of functional deficits by providing a critical analysis of nerve damage in order to effectively devise and implement repair techniques for PBI. Blast-induced neurotrauma is a common injury modality associated with the current war efforts and increasing levels of terrorist activity (1-3). Exposure to the primary pressure wave generated by explosive devices causes significant neurological deficits and is responsible for many of the war related pathologies during Operation Iraqi Freedom and the Global War on Terror. PBI in the central nervous system (CNS) causes neuronal death and leads to decreased neurological function. Following the initial impact trauma, the secondary biochemical response associated with neurotrauma, such as the production of free radicals and the increased expression of acrolein (a known neuronal toxin), further degrades the injury site. (4) Despite the far-reaching effects of the aforementioned debilitating disorders, the underlying mechanisms governing the functional loss associated with the CNS are poorly understood. Previously established animal models for blast injury have analyzed global responses, but lack an understanding of the physical injury and the primary and secondary response mechanisms at the tissue level (5-7). Poor characterization of these reactions prevents adequate intervention and treatment. Therefore, appropriate understanding of the mechanisms involved in blast injury is paramount for increasing soldier survivability and treating afflicted individuals. The current study introduces several novel ex vitro techniques to model the effects of PBI in an attempt to elucidate the mechanisms of blast injuries on the CNS, particularly in relation to spinal cord tissue. For this study, a blast wave generator was created to model an improvised explosion in order to create a reproducible and controllable degree of injury for analysis. Functional and anatomical deficits resulting from blast exposure will be continuously monitored using an electrophysiological recording apparatus to characterize neurological activity and a dye-exclusion assay to quantify axonal membrane integrity.