Neurological Effects Of A Single Low Level Blast Overpressure Exposure : Behavior And Micro RNA Mechanisms Of Mild Traumatic Brain Injury In A Rodent Model

ECU Author/Contributor (non-ECU co-authors, if there are any, appear on document)

Dorothy L. Dobbins (Creator)

Institution

East Carolina University (ECU )

Web Site: http://www.ecu.edu/lib/

Abstract: The increased use of explosive devices within warfare and acts of terrorism has allowed blast overpressure exposure (BOE) to become a significant concern. The most common wound sustained by BOE is blast-induced mild traumatic brain injury (mTBI). These injuries involve no gross physical damage to the brain and evolve over time. The late manifestation of neuropsychiatric symptoms combined with no observable physical damage allows these injuries to largely remain undiagnosed or misdiagnosed for other mental disorders. This study aims to understand the effects of blast-induced neurotrauma and possibly improve diagnostics for these injuries. Anesthetized subjects were exposed to a single low-level blast overpressure of 10-12 psi. Behavioral assessments were performed at various time points to assess the evolution of blast-induced mTBIs. Micro RNAs (miRNAs) were extracted from whole blood and assessed for any changes in gene expression at 24 hours, one week, one month, and two months after BOE. Morris water maze testing at 1 and 2 months after BOE was used to examine behavioral changes associated with BOE. Blasted subjects exhibited increased depression and impairments to learning and memory at one month but these changes were absent by two months after injury. Molecular assessments revealed five miRNAs commonly dysregulated across time points, miR- 27a, 30a, 34c, 449a and let-7c. The functional impact of these miRNAs was determined through pathway analysis using DAVID and GOrilla. Aberrant miRNA expression was found to regulate increased neurogenesis, synaptogesis, synaptic plasticity, long-term potentiation and apoptosis. The miRNA mediated gene network regulation may be an attributing factor to neuropsychiatric symptoms and behavioral changes observed in blasted subjects. Temporal changes in miRNA expression and behavior provide a better understanding of blast-induced mTBI sequelae. Identified miRNAs induced by blast exposure have the potential to improve diagnostic and therapeutic strategies.

Additional Information

Publication

Thesis

Language: English

Date: 2023

Subjects

Biology;Molecular biology;Neuroscience;Bioinformatics;Depression;Mild traumatic brain injuries;MiRNAs;Morris water maze

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