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Ear Level Cooling for Otoprotection

耳部冷却以保护耳部

基本信息

批准号：
10433343
负责人：
Christopher Spankovich
金额：
$ 23.25万
依托单位：
UNIVERSITY OF MISSISSIPPI MED CTR
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-03-01 至 2024-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10433343
关键词：
Acute Alternative Therapies Aluminum Animal Model Animals Antibodies Apoptotic Audiology Auditory BODIPY Black race Bolus Infusion CASP3 gene Cavia Cell Death Cells Cellular Stress Cisplatin Cochlea Cochlear Implants Cochlear duct Code Complementary therapies Coupled Devices Dose Ear Engineering Exposure to External auditory canal FDA approved Fluorescence Free Radicals Functional disorder Hair Cells Heart Injuries In Situ Hybridization Individual Inductively Coupled Plasma Mass Spectrometry Injections Injury to Kidney Irrigation Lipid Peroxidation Lipids Literature Long-Evans Rats Mass Spectrum Analysis Measures Mediating Metabolic Methods Modeling Molecular Biology Nervous System Trauma Neurons Neurosciences Noise Pathology Pathway Analysis Pathway interactions Pharmaceutical Preparations Pharmacology Platinum Predisposition Prevention Protein Binding Domain RNA Binding RNA-Binding Proteins Rat-1 Rattus Regimen Research Research Design Role Sensorineural Hearing Loss Series Testing Therapeutic Thinking Time Tissue imaging Tissues Toxin Transcript Translating Translations Up-Regulation Water Work animal imaging base cisplatin induced hearing loss cisplatin-DNA adduct clinical translation cohort cold shock protein confocal imaging experimental study guinea pig model hearing preservation iatrogenic injury model design natural hypothermia novel otoprotectant ototoxicity prevent protective effect response time use tool uptake

项目摘要

ABSTRACT We previously demonstrated significant protection from cisplatin induced hearing loss using cool water ear canal irrigation. However, the study was limited to a single bolus injection of cisplatin and acute time period (Spankovich et al. 2016). More recently, we examined application of localized cooling of the ear canal with repeated doses of cisplatin, over an expanded period of time, and using an alternative method of cooling (ear bar cooled by a Peltier device). Here, we propose to advance our novel application of localized ear cooling in mitigation of drug induced hearing loss; which we call Cool OtOprotective ear Lumen (COOL) therapy. Hypotheses: We hypothesize that (1) our COOL therapy will show protection in a rat model; (2) protection from our COOL therapy is mediated by reduced cochlear uptake of cisplatin, expression or cold shock proteins, and reduced upstream and downstream cell apoptotic cell death pathways; (3) that we will observe protection from vestibular damage with our COOL therapy. Specific Aims: Aim 1. To determine whether COOL therapy reduces cisplatin uptake and auditory-vestibular pathology, increases the expression of transcripts that code for cold-shock proteins, and reduced cellular stress pathways. Study Design: For Aim 1, Guinea pig and Long Evans rats will be exposed to cisplatin while undergoing COOL therapy and compared to sham controls and warmed animals. Aim 1(a) will determine if our findings translate to another species (rat) and explore vestibular effects. Aim 1(b) will examine antibody immunostaining for cisplatin DNA-adducts, mass spectrometry measured platinum concentrations in cochlear tissue, and confocal images of animals treated with fluorescent tagged cisplatin. Aim 1(c,d) will examine expression of cold shock proteins and evidence of lipid perioxidation and caspase-3 activation.

摘要