Date of Award
Master of Science (MS)
Basic Medical Sciences
Committee Member 1
Bradley S. Duerstock
Blast injury has been coined the "signature injury of the Iraq war" resulting in a surge of interest in understanding and addressing the corresponding pathological sequelae. As modern warfare develops into a distinctly guerrilla style combat by smaller terrorist groups against larger, regimented forces, tactics like suicide bombing and roadside bombing with Improvised Explosive Devices (IEDs) become more prevalent. 1,2 This increased use of IEDs countered with improved body armor and protective technologies has significantly increased the survival rate of such attacks. 1.2 However, as survival rates have improved with body armor and other protective technologies, the incidence of reported head and neck injuries has increased2 and with it the incidence of long term cognitive, emotional, social and attentional deficits. These symptoms and disorders are not limited to the battlefield; these are the same veterans who eventually return home and often have difficulty coping with transition to civilian life and a better understanding of the mechanisms and etiology of these disorders should assist in early intervention strategies to improve long-term recovery outcomes.
Our lab has developed an animal model for blast injury using a compressed air chamber to deliver rapid explosive-like shock-wave exposures. The data shown here demonstrate physical, behavioral and biomarker based metrics used to evaluate the clinical relevance and severity of our injury model. The physical evaluation consisted of dynamic pressure transducer measurements to verify the range-dependent peak overpressure elicited by the blast. Following some initial evaluation of different exposure intensities, a mild blast was chosen for further analysis as a model surrogate for nonlethal blast exposure. Behavioral analysis using both an open-field exploration box and rotarod demonstrated no significant, gross motor deficits resulting from blast injury. However, further analysis using a tail swing tests suggest this injury model elicits significant depression-like symptoms compared to controls. Tissue and systemic-level examination for evidence of stress included assays for corticotrophin releasing factor(CRF), a known factor in neural circuits for anxiety and depression, and acrolein bound protein adducts in tissue and urine, markers of oxidative stress, indicative of membrane damage and lipid peroxidation. All three of these measured significant elevation in blast exposed animals. Imaging of extravasations of serum albumin, elevated in blast exposed animals indicated a possible mechanism of injury to the brain via inflammatory response to a foreign agent.
This model represents an avenue for examining the etiology of blast induced neurotrauma, biomarkers for early detection, and evaluation of potential treatment strategies to alleviate long-term deficits which may arise from secondary injury mechanisms like oxidative stress and neuroinflammatory responses.
Walls, Michael Kelso, "A Rat Model Of Mild Blast-Induced Head Trauma With Structural And Biochemical Abnormalities In The Absence Of Motor Deficits" (2014). Open Access Theses. 279.