Document Type

Dissertation

Date of Award

8-31-2021

Degree Name

Doctor of Philosophy in Biomedical Engineering - (Ph.D.)

Department

Biomedical Engineering

First Advisor

N. Chandra

Second Advisor

Bryan J. Pfister

Third Advisor

Antje Ihlefeld

Fourth Advisor

Bruce A. Citron

Fifth Advisor

Kelvin Y. Kwan

Sixth Advisor

Rong Zhu Gan

Abstract

Exposure to blast causes debilitating trauma including tinnitus among soldiers and civilians (Cave et al., 2007; Remenschneider et al., 2014; Singh et al., 2016). Tinnitus is a constant ringing noise perception without external acoustic event; it affects sleep, concentration, behavior, leading to suicidal tendencies (Swan et al., 2017). Though blast induced tinnitus has been studied, structural and functional dysfunctions along auditory systems have not been systematically studied. It was hypothesized in this work that blast causes tinnitus even while the ears are mechanically protected, and the damage occurred in both central and peripheral auditory systems, which contributed to increased anxiety and sleep deficits.

Sprague Dawley rats (40-60-thy-old male) exposed to 180 kPa were used as the mild blast animal model. Acoustic Startle Response (ASR) distinguished hearing loss from tinnitus. The morphology of the hair cells in the peripheral auditory system (PAS) was visualized by myosin VIIA immunohistochemistry. Distortion Product Otoacoustic Emission (DPOAE) evaluated the function of outer hair cells (OHCs). The sensory bridge between PAS and central auditory system (CAS) was investigated through Auditory Brainstem Response (ABR). Further, in CAS, immunohistochemistry was conducted in inferior colliculus (IC), geniculate body (GB) and auditory cortex (AC) to examine the excitatory and inhibitory neurotransmitter receptor expression levels. Sleep condition and anxiety level welt evaluated using piezoelectric sleep detector and Elevated Plus Maze, respectively.

It was found that 180 kPa mild blast with the protection of earplugs induced tinnitus like symptoms and hyperacusis after injury both acutely and progressively. Earplugs protected the tympanic membrane from being ruptured while they only marginally prevented tinnitus. In PAS, OHCs were both structurally and functionally disrupted by mild blast Sustained elevation of ABR threshold was also observed, indicating that blast impairs the neuronal circuity between cochlea and IC, more severely in the acute conditions. In CAS, enhanced neuronal inhibition was exhibited in AC and GB while increased excitation was displayed in IC. Blast in our animal model induced sleep patterns shift and anxiety. Thus, this study concluded that blast caused tinnitus even with the protection of earplugs, and the pathological damage occurred in both PAS and CAS, validating the hypothesis. These findings guided the design of future protection gears and provided insights to the therapeutic intervention development.

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