A Novel Preclinical Model of Moderate Primary Blast-Induced Traumatic Brain Injury

Abstract

Blast-induced traumatic brain injury (bTBI) is the signature injury of the recent Iraq and Afghanistan wars. Here, we present a novel method to induce bTBI using shock wave (SW) lithotripsy. Using a lithotripsy machine, Wistar rats (N=70; 408.3 +/- 93g) received five SW pulses to the right side of the frontal cortex at 24kV and a frequency of 60Hz. Animals were then randomly divided into three study endpoints: 24h (n=25), 72h (n=19) and 168h (n=26). Neurological and behavioral assessments (Garcia's test, beam walking, Rotarod, and elevated plus maze) were performed at the baseline, and further assessments followed at 3, 6, 24, 72, and 168h post-injury, if applicable. We performed digital subtraction angiography (DSA) to assess presence of cerebral vasospasm due to induced bTBI. Damage to brain tissue was assessed by an overall histological severity (OHS) score based on depth of injury, area of hemorrhage, and extent of axonal injury. Except for beam walking, OHS was significantly correlated with the other three outcome measures with at least one of their assessments during the first 6h after the experiment. OHS manifested the highest absolute correlation coefficients with anxiety at the baseline and 6h post-injury (r(baseline)=-0.75, r(6hrs)=0.85; p<0.05). Median hemispheric differences for contrast peak values (obtained from DSA studies) for 24, 72, and 168h endpoints were 3.45%, 3.05% and 0.2%, respectively, with statistically significant differences at 1 versus 7d (p<0.05) and 3 versus 7d (p<0.01). In this study, we successfully established a preclinical rat model of bTBI with characteristics similar to those observed in clinical cases. This new method may be useful for future investigations aimed at understanding bTBI pathophysiology.