| dc.description.abstract | Even with the use of hearing protection devices (HPDs), hearing damage caused by blast exposure dominates service-related disabilities faced by active service members and Veterans. Epidemiology studies have revealed that this hearing damage is associated with traumatic brain injury (TBI). There is a need to further investigate the mechanisms of the formation and prevention of auditory hearing damage. Liraglutide, a GLP-1R agonist, has been found to be a potential treatment for TBI-induced memory deficits. Our previous studies have focused on the therapeutic effect of liraglutide in the prevention and recovery from repeated low-intensity blast exposure. This thesis focuses on the therapeutic function of liraglutide after exposure to higher-level blasts associated with TBI using the chinchilla animal model with HPDs.
In this study, chinchillas were separated into 3 groups: pre-blast treatment, post-blast treatment, and blast control. All groups were exposed to 3 blasts at the blast overpressure (BOP) level equivalent to mild-TBI (15-20 psi or 103-138 kPa) on Day 1 with their ears protected with HPDs (e.g., earplugs). Chinchillas were observed for either 14 or 28 days after blast. To determine the state of the auditory system, hearing function tests including auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) were conducted prior to blast exposure, after blast exposure, and on Days 4, 7, 14, and 28. Upon the completion of the experiment, the cochlea and brain tissues were collected for immunofluorescence studies.
The measurements collected from ABR and DPOAE recordings as well as immunofluorescence results indicated that liraglutide was able to significantly prevent acute blast-induced hearing damage and potentially aid in recovery post-blast exposure.
The work presented in this thesis improves our understanding of the effect of higher-level blast exposure on the auditory system and the therapeutic effect of liraglutide. Future work includes improving statistical analyses and investigation of the mechanisms by which liraglutide works in auditory injury prevention and restoration. | en_US |
