Access Type

Open Access Thesis

Date of Award

January 2015

Degree Type

Thesis

Degree Name

M.S.

Department

Biomedical Engineering

First Advisor

Srinivasu Kallakuri

Second Advisor

John Cavanaugh

Abstract

Blast induced neurotrauma (BINT) is the signature wound of veterans returning from various military operations. A substantial percentage of Operations Enduring Freedom (OEF) and Iraqi Freedom (OIF) veterans have reported to experience ongoing or new pain following their military service. Head (58%) and back (55%) have been the high prevailing locations of pain in these returning OIF and OEF veterans and the underlying pathomechanism of these conditions is yet to be understood. In the context of blast overpressure induced pathological changes, the fundamental question that still needs to be addressed is whether there are any underlying cellular injury changes the spinal cord following blast. If proven, it is postulated that cellular injury changes in the form of glial activation may contribute to neuronal sensitization and altered sensation through the release of various inflammatory mediators. Much of the previous and ongoing research studies have been directed at understanding blast induced changes in the brain alone with changes in the spinal cord still remaining an enigma. Accordingly, as a first step, we attempted to investigate spatial and temporal alterations in glial activation in the spinal cord following blast exposure. In addition, we also attempted to study the presence of axonal injury in the cervical spinal cord following blast overpressure.

As part of this investigation, anaesthetized male Sprague Dawley rats were subjected to a single insult of blast overpressure (22psi)using a helium driven shock tube. The rats were divided into two groups; Sham and Blast with acute and sub-acute survival periods; 6hrs, 24hrs, 3days and 7days respectively. Glial activation was assessed by GFAP (Glial Fibrillary Acidic Protein) and IBA1 (Ionized Calcium Binding Molecule 1) immunohistochemistry. GFAP and Iba1 are routinely used to investigate astrocytic and microglial activation in the brain and spinal cord. Axonal injury in the cervical spinal cord was assessed by β-APP (Beta Amyloid Precursor Protein) immunohistochemistry. β-APP is a commonly used marker to detect the presence of diffuse axonal injury in the brain.

Behaviorally, blast exposed rats exhibited significantly increased surface righting duration compared to sham rats. Our immunohistochemistry results indicate differential activation of astrocytes and microglia in various spinal cord regions in blast exposed group compared to sham. Rats subjected to blast overpressure showed increased expression of astrocytes and microglia at acute and sub-acute periods. Evidence of diffuse axonal injury also observed in the cervical spinal cord following the blast overpressure. Taken together, our results suggest that blast exposure in a craniocephalic orientation in rats resulted an enhanced spinal glial reactivity as well as cervical spinal axonal injury. We postulate that injury changes in the form of activation of astrocytes and microglia with diffuse axonal injury may contribute to the release of various inflammatory mediators which may in turn be related to the ensuing sensory changes. These results lay foundation to further studies on blast related injury changes in the spinal cord.

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