Novel Model to Investigate Blast Injury in the Central Nervous System

Abstract

Blast-induced neurotrauma (BINT) is a common injury modality associated with the current war efforts and increasing levels of terrorist activity. Exposure to the primary blast wave generated by explosive devices causes significant neurological deficits and is responsible for many of the war-related pathologies. Despite research efforts, the mechanism of injury is still poorly understood. To this end, we have established a novel ex vivo model for the direct observation and quantification of BINT at the tissue level. The model provides a quantifiable and reproducible method to illustrate the mechanism of BINT. Isolated sections of guinea pig spinal cord white matter were exposed to a supersonic shockwave using a blast generator with small-scaled explosives. The blast wave impact with isolated tissue was observed using focused shadowgraphy with a high-speed camera recording at 90,000 fps. Concurrently, functional deficits were measured by monitoring the production of compound action potentials using a double sucrose gap-recording chamber. Additionally, anatomical deficits were measured after blast exposure with a dye exclusion assay to visualize axonal membrane permeability. Our findings demonstrate that direct exposure to the blast wave compressed nervous tissue at a rate of 60 m/sec and led to significant functional deficits. Damage to the isolated spinal cord was marked by increased axonal permeability, suggesting rapid compression from the shockwave-generated high strain rates that resulted in membrane disruption. The model provides new insight into the mechanism of BINT and permits direct observation that may contribute to the development of appropriate treatment regimens.