TY - JOUR
T1 - A Novel Preclinical Model of Moderate Primary Blast-Induced Traumatic Brain Injury
AU - Divani, Afshin A.
AU - Murphy, Amanda J.
AU - Meints, Joyce
AU - Sadeghi-Bazargani, Homayoun
AU - Nordberg, Jessica
AU - Monga, Manoj
AU - Low, Walter C.
AU - Bhatia, Prerana M.
AU - Beilman, Greg J.
AU - Santacruz, Karen S.
N1 - Publisher Copyright:
© Copyright 2015, Mary Ann Liebert, Inc. 2015.
PY - 2015/7/15
Y1 - 2015/7/15
N2 - 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±93 g) received five SW pulses to the right side of the frontal cortex at 24 kV and a frequency of 60 Hz. Animals were then randomly divided into three study endpoints: 24 h (n=25), 72 h (n=19) and 168 h (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 168 h 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 6 h after the experiment. OHS manifested the highest absolute correlation coefficients with anxiety at the baseline and 6 h post-injury (rbaseline=-0.75, r6hrs=0.85; p<0.05). Median hemispheric differences for contrast peak values (obtained from DSA studies) for 24, 72, and 168 h endpoints were 3.45%, 3.05% and 0.2%, respectively, with statistically significant differences at 1 versus 7 d (p<0.05) and 3 versus 7 d (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.
AB - 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±93 g) received five SW pulses to the right side of the frontal cortex at 24 kV and a frequency of 60 Hz. Animals were then randomly divided into three study endpoints: 24 h (n=25), 72 h (n=19) and 168 h (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 168 h 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 6 h after the experiment. OHS manifested the highest absolute correlation coefficients with anxiety at the baseline and 6 h post-injury (rbaseline=-0.75, r6hrs=0.85; p<0.05). Median hemispheric differences for contrast peak values (obtained from DSA studies) for 24, 72, and 168 h endpoints were 3.45%, 3.05% and 0.2%, respectively, with statistically significant differences at 1 versus 7 d (p<0.05) and 3 versus 7 d (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.
KW - Axonal damage
KW - Blast traumatic brain injury
KW - Brain injury
KW - Functional outcomes
KW - Lithotripsy
KW - Vasospasm
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U2 - 10.1089/neu.2014.3686
DO - 10.1089/neu.2014.3686
M3 - Article
C2 - 25585201
AN - SCOPUS:84934282638
SN - 0897-7151
VL - 32
SP - 1109
EP - 1116
JO - Journal of neurotrauma
JF - Journal of neurotrauma
IS - 14
ER -