Acoustic overstimulation or hypertension modulates cochlear blood flow, causing temporary and reversible microischemia in the stria vascularis. Strial microischemia is characterized by irregularity in vessel diameters and elevated permeability, i.e. strial micro-leakage. Cochlear ischemia alone may cause abrupt hearing loss and tinnitus. Combined strial micro-leakage and systemic administration of aminoglycoside antibiotics can escalate aminoglycoside strial trafficking, and presumptively its ototoxicity. In this proposal, we will determine which risk factors, including sound exposure, hypertension or age can induce strial micro-leakage, and establish a reliable ototoxic mouse model.
The specific aims of this project are to:
Aim 1 : validate a noise-induced strial micro-leakage mouse model. We will determine the acoustic stimulation conditions that reliably induce strial micro-leakage (e.g., single dose, interrupted sound exposures).
Aim 2 : determine the effect of hypertension or age in inducing strial micro-leakage, by increasing blood volume in CBA/CaJ mice. In addition, we will examine effect of age on strial micro-leakage in C57BL/6 mice, a strain with early onset of age-related hearing loss.
Aim 3 : determine if vasoactive reagents prevent strial micro-leakage. We will use vasodilators or vasoconstrictors to regulate the strial blood flow and determine if they reduce micro-leakage. The outcome of this project will establish a reliable mouse model for strial micro-leakage. This is important as microischemia may underlie several factors that increase the risk of ototoxicity, such as hypertension or poor blood flow. In addition, we seek to identify potential interventions to pharmacologically minimize strial microischemia, and reduce the risk of ototoxicity.

Public Health Relevance

Acoustic overstimulation or hypertension modulates cochlear blood flow, causing temporary and reversible microischemia in the stria vascularis. Combination of cochlear microischemia and systemic administration of aminoglycoside antibiotics can escalate aminoglycoside intra-strial trafficking, and consequently its ototoxicity. The proposed research will determine several risk factors on strial microischemia, and establish a reliable ototoxic mouse model.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Small Research Grants (R03)
Project #
5R03DC011622-03
Application #
8429492
Study Section
Special Emphasis Panel (ZDC1-SRB-Y (58))
Program Officer
Freeman, Nancy
Project Start
2011-03-01
Project End
2015-02-28
Budget Start
2013-03-01
Budget End
2015-02-28
Support Year
3
Fiscal Year
2013
Total Cost
$146,300
Indirect Cost
$51,300
Name
Oregon Health and Science University
Department
Otolaryngology
Type
Schools of Medicine
DUNS #
096997515
City
Portland
State
OR
Country
United States
Zip Code
97239
Jiang, Meiyan; Wang, Qi; Karasawa, Takatoshi et al. (2014) Sodium-glucose transporter-2 (SGLT2; SLC5A2) enhances cellular uptake of aminoglycosides. PLoS One 9:e108941
Li, Hongzhe; Wang, Qi; Steyger, Peter S (2011) Acoustic trauma increases cochlear and hair cell uptake of gentamicin. PLoS One 6:e19130