# Mechanisms of Blast-Induced Vestibular Injury

> **NIH NIH R01** · UNIVERSITY OF MISSISSIPPI MED CTR · 2022 · $352,894

## Abstract

Project Summary
 The application is in respond to opportunity announcement NOT-AG-21-018 “Alzheimer's-
focused administrative supplement for NIH grants that are not focused on Alzheimer's disease.
The goal of our current funded project (R01DC018919) is to elucidate the mechanisms underlying
blast-induced vestibular injury in a rat model. The supplement is to expand the current study to
investigate the impact of blast exposure through the ear canal on the development of traumatic
brain injury (TBI) and Alzheimer's disease (AD) pathology. As air-filled structures and directly
exposed to the surrounding air, the unprotected ears are among the most frequently damaged
sites during blast exposure. Although clinical studies reported that there is an association
between tympanic membrane perforation and TBI in blast exposure victims, it remains
controversial whether the acoustic meatus serves as conduit the primary blast wave affects the
brain. Our current funded project has developed a novel blast rat model in which blast waves are
directly delivered into the rodent ear canal while avoiding confounding complications. Using this
model, we found that ear-conducted blast waves not only cause inner ear vestibular damage, but
also cause substantial neurophathological changes in the brain including profound chronic
neuroinflammatory response, macrophage filtration that could be due to increased blood-brain
barrier (BBB) permeability, and deficits in learning and memory. Activation of microglia and
cerebrovascular damage have been implicated in the development and progression of AD
pathology. The results lead to our hypothesis that the unprotected ears provide a vulnerable locus
for blast waves to damage the brain; shock waves primarily delivered through the ear canal trigger
an acute and chronic inflammatory response and cerebrovascular dysfunction that exacerbate
AD pathogenesis. The supplement application will take the advantage of the current ear blast
model to further investigate the neuroinflammatory responses, cerebrovascular pathology and AD
biomarkers in the brain and the behavioral consequences following ear blast exposure in non-
transgenic wild type rats and in TgF344-AD rats, a widely used transgenic rat model for AD.
Whether blast exposure via ear accelerates AD pathogenesis of the TgF344-AD rats will be
determined. Results from the proposed experiments will lead to better understanding of the role
of unprotected ears in the development of blast-induced TBI and AD and provide the scientific
basis for mandating ear protection in blast-prone locations, such as battlefields and training or
industrial environments, because ear protection is not only to protect our hearing and balance,
but also to protect us from blast-induced brain injury which may trigger AD in later life.

## Key facts

- **NIH application ID:** 10498137
- **Project number:** 3R01DC018919-02S1
- **Recipient organization:** UNIVERSITY OF MISSISSIPPI MED CTR
- **Principal Investigator:** WU ZHOU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $352,894
- **Award type:** 3
- **Project period:** 2020-09-11 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10498137

## Citation

> US National Institutes of Health, RePORTER application 10498137, Mechanisms of Blast-Induced Vestibular Injury (3R01DC018919-02S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10498137. Licensed CC0.

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