A Novel Method to Induce Blast Traumatic Brain Injury in Rodents (P6.083)

Objective: Our study aimed to develop a novel animal model of blast induced traumatic brain injury (bTBI) that simulates blast injury by generating localized bTBI in a laboratory setting using shockwave lithotripsy. Background: Increased use of explosives in recent wars has led to higher incidences of bTBI, but currently there is no existing animal model of bTBI that produces characteristics of blast injury in clinical settings. Methods: Using a lithotripsy machine, Wistar rats (N=70, 408.3±93 grams) received 5 shockwave pulses to the right frontal cortex. Animals were randomly assigned to three study endpoints: 24 hours (n=25), 72 hours (n=19) and 168 hours (n=26). Neurological and behavioral assessments (Garcia test, beam walking, and elevated plus maze) were performed at endpoints, with further assessments at 3, 6, and 24 hours post-injury. We performed digital subtraction angiography (DSA) to assess cerebral vasospasms due to bTBI. Brain tissue damage was assessed by an overall histological severity (OHS) score based on depth of injury, area of hemorrhage, and extent of axonal injury. Results: Except for beam walking, OHS was significantly correlated with the other three outcome measures with at least one measurement during the first six hours after the experiment. OHS manifested the highest absolute correlation coefficients with anxiety at the baseline and 6 hours post injury (rbaseline=-0.75, r6-hrs=0.85; P<0.05). Median hemispheric differences for contrast peak values (obtained from DSA studies) for 24, 72, and 168 hours endpoints were 3.45[percnt], 3.05[percnt] and 0.2[percnt], respectively, with statistically significant difference at 1 vs. 7 (P<0.05) and 3 vs. 7 (P <0.01) days. Conclusions: In this study, we successfully established a preclinical rat model of bTBI with characteristics similar to those observed in clinical cases. This model may be useful for future investigations aimed at understanding bTBI pathophysiology. Disclosure: Dr. Hevesi has nothing to disclose. Dr. Bachour has nothing to disclose. Dr. Safinia has nothing to disclose. Dr. Sweis has nothing to disclose. Dr. Divani has nothing to disclose.