Session: 16-01-01: Poster Session: NSF-Funded Research (Grad & Undergrad)

Paper Number: 99829

99829 - Repeated Mild Brain Injury Induced by Blast and Acceleration: A Comparative Study 

Introduction: Mild traumatic brain injury (mTBI) is a serious public healthcare issue. Most of head injuries in car accidents, sports, and military are categorized as mild, and they often occur in a repeated fashion over a few minutes to a few years, collectively known as Repeated Mild Traumatic Brain Injury (rmTBI). Some individuals develop long-term disabilities because of rmTBI, including memory and motor function impairment. Animal modeling of rmTBI can be used to understand the mechanism of injury and for preclinical drug development studies. We developed injury models resulting in rmTBI in rats. The goal of this study was to compare the consequences of the type of rmTBI on brain pathology and behavioral functions.

Methods: Two rmTBI models are presented in this work: 1) blast-induced TBI (bTBI), 2) acceleration-induced TBI with whole-body deceleration (WBD). A compressed-gas-driven shock tube was used to replicate bTBI in rats with a rapid overpressure of 270 kPa for the duration of 1.6 ms. Either one impact or three impacts were applied to assess the effect of repeated injuries. In the WBD apparatus, rats were secured to a horizontal track and a rapid deceleration with 80 g peak was applied from initial velocity of 12 m/s. Three consecutive impacts were applied. We tested male Sprague-Dawley rats assigned to two groups of injury and sham (only anesthesia), and impacted them dorsoventrally (n=8). We used a battery of behavioral tests within 20 days post-injury including Rotarod to assess motor function and Novel Object Recognition (NOR) for memory. We studied the effects of injury on brain histology after 7- or 21-days post-injury. We used immunofluorescence (IF) staining to assess Iba-1 expression as a biomarker for microglial activation. We also assessed TLR4 with RT-PCR and tau proteins with Western Blot to assess the inflammatory response.

Results: In both bTBI and WBD injury models IF straining of Iba-1 in the frontal cortex was significantly increased. This increase was higher for multiple blast compared to single (factor of 2.9 vs. 2.5) and was higher for repeated blast compared to WBD (factor of 2.9 vs. 1.3).  Accumulation of pTau protein (S396) was higher for multiple blast compared to single blast (factor of 2.8 vs. 1.9). RT-PCR showed a significant increase in TLR4 in WBD (factor of 4 vs. 1) seven days after the injury (p=0.029), and no significant difference after 21 days.

Rotarod results showed higher values of reduction in time at fall (TAF) in all days post-injury due to multiple bTBI compared to WBD. Both injury models caused significant reductions in TAF compared to their respective shams. NOR detected memory deficit increasingly on days 5, 9, and 15 after WBD injury and signs of recovering on day 20. The measurement used was discrimination index (DI) defined as the difference in time spent by each rat with the novel and the familiar objects divided by the total time spent exploring both objects.

 

Conclusions: Our results demonstrate the expression of histological biomarkers for rmTBI in short-term (within 7 days post-injury) but not conclusive in long-term (day 21). On the other hand, behavioral tests were effective to detect long-term deficits and indicate recovery. Blast and WBD can result in different patterns of deformation in brain. Blast causes mainly pressure waves propagating through the whole brain and WBD causes coup-countercoup regions of high stress and strain. The biomarkers and behavioral measures used in this study showed varied changes in brain pathology and function due to blast or WBD injury. These differences can be used to improve our understanding of the biomechanics of brain deformation and tissue damage.

 

Presenting Author: Sheida Vafadar Temple University

Presenting Author Biography: I am a PhD candidate in Mechanical Engineering at Temple University. I also have a Master’s degree in Biomechanical engineering. <br/>My PhD research focuses on studying traumatic brain injury and assessing new treatment options, I am also simulating a finite element model of the brain.

Authors:

Sheida Vafadar Temple University
Hongbo Li Lewis Katz School of Medicine at Temple University
Soroush Assari Temple University
Dianne Langford Lewis Katz School of Medicine at Temple University
Sara J. Ward Lewis Katz School of Medicine at Temple University
Ronald F. Tuma Lewis Katz School of Medicine at Temple University
Kurosh Darvish Temple University