Citation

Divani AA, Murphy AJ, Meints J, Sadeghi-Bzargani H, Nordberg J, Monga M, Low WC, Bhatia PM, Beilman GJ, SantaCruz KS. J. Neurotrauma 2015; 32(14): 1109-1116.

Affiliation

University of Minnesota, Neurology , 420 Delaware Street SE , MMC 295 , Minneapolis, Minnesota, United States , 55455 ; adivani@gmail.com.

Copyright

(Copyright © 2015, Mary Ann Liebert Publishers)

DOI

10.1089/neu.2014.3686

PMID

25585201

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 shockwave (SW) lithotripsy. Using a lithotripsy machine, Wistar rats (N=70, 408.3±93 grams) received 5 SW pulses to the right side of the frontal cortex at 24 kV and a frequency of 60 Hz. Animals were then randomly assigned to three study endpoints: 24 hours (n=25), 72 hours (n=19) and 168 hours (n=26). Neurological and behavioral assessments (Garcia's test, beam walking, Rotarod, and elevated plus maze) were performed at the endpoints, and further assessments followed at 3, 6, 24, 72, and 168 hours 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 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%, 3.05% and 0.2%, respectively, with statistically significant difference at 1 vs. 7 (P<0.05) and 3 vs. 7 (P <0.01) days. 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.

Language: en