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Efficacy and Mechanisms of Mild Therapeutic Hypothermia for Hearing Preservation from NIHL

Award Number: F31DC018212
ORGANIZATION: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 01/09/2020
PERIOD OF PERFORMANCE END DATE: 11/08/2022

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Efficacy and Mechanisms of Mild Therapeutic Hypothermia for Hearing Preservation from NIHL - Project Summary Noise-induced hearing loss (NIHL) caused by exposure to intense or repeated noise results in damage to the sensitive structures within the cochlea. NIHL has become one of the leading occupational and recreational hazards afflicting nearly 40 million Americans. NIHL is also a serious concern for our military, and overall results in a high economic burden due to worker compensation and veteran disability. Although many treatments have been proposed to mitigate NIHL with promising results in preclinical studies, there are still no FDA-approved treatments for NIHL. Mild therapeutic hypothermia (30-33 °C) has been extensively studied as a neuroprotective strategy against various types of neurological traumas because of its ability to mediate various injury responses to trauma including oxidative stress, apoptosis, and inflammation. We aim to assess the therapeutic benefit of localized therapeutic hypothermia in mitigation of cochlear injury following acoustic trauma in a rodent model. In this proposal, we seek to engineer a novel non-invasive device used to induce localized mild therapeutic hypothermia post-NIHL and assess long-term functional hearing and cochlear neural substrate preservation. Our preliminary results suggest that controlled and localized therapeutic hypothermia provided to the inner ear post-NIHL significantly lowers hearing threshold shifts in hypothermia-treated animals when compared to normothermic control animals. Furthermore, we observe reduced cochlear synaptopathology with therapeutic hypothermia. To determine protective mechanisms underlying hypothermia, we will identify molecular pathways and gene networks that are regulated by temperature post-NIHL. A detailed characterization of the pathways in a relevant rodent model will provide future opportunities to identify additional synergistic otoprotective targets. Based on preliminary results, our primary mechanistic emphases will be on caspase-dependent apoptotic pathways and inflammatory responses with activated macrophage recruitment and expression. In the long-term, we aim to address the limited therapeutic options for NIHL that may be extended to various otological traumas, including blast-induced hearing loss or surgically-induced hearing loss.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2023 ( Subtotal = -$17,638 )
2023	2022	UNIVERSITY OF MIAMI	1320 SOUTH DIXIE HIGHWAY STE 650	CORAL GABLES	FL	33146	MIAMI-DADE	USA	Research Related to Deafness and Communication Disorders	000	3	9/27/2023	NON-COMPETING CONTINUATION	-$17,638
														Subtotal = -$17,638

Issue Date FY: 2022 ( Subtotal = $41,627 )
2022	2022	UNIVERSITY OF MIAMI	1320 S DIXIE HWY STE 650	CORAL GABLES	FL	33146	MIAMI-DADE	USA	Research Related to Deafness and Communication Disorders	000	3	12/21/2021	NON-COMPETING CONTINUATION	$41,030
2022	2022	UNIVERSITY OF MIAMI	1320 S DIXIE HWY STE 650	CORAL GABLES	FL	33146	MIAMI-DADE	USA	Research Related to Deafness and Communication Disorders	002	3	4/25/2022	NON-COMPETING CONTINUATION	$598
2022	2022	UNIVERSITY OF MIAMI	1320 S DIXIE HWY STE 650	CORAL GABLES	FL	33146	MIAMI-DADE	USA	Research Related to Deafness and Communication Disorders	003	3	5/19/2022	NON-COMPETING CONTINUATION	-$1
2022	2022	UNIVERSITY OF MIAMI	1320 S DIXIE HWY STE 650	CORAL GABLES	FL	33146	MIAMI-DADE	USA	Research Related to Deafness and Communication Disorders	001	3	1/26/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $41,627

Issue Date FY: 2021 ( Subtotal = $46,036 )
2021	2021	UNIVERSITY OF MIAMI	1320 S DIXIE HWY STE 650	CORAL GABLES	FL	33146	MIAMI-DADE	USA	Research Related to Deafness and Communication Disorders	001	2	2/2/2021	NON-COMPETING CONTINUATION	$516
2021	2021	UNIVERSITY OF MIAMI	1320 S DIXIE HWY STE 650	CORAL GABLES	FL	33146	MIAMI-DADE	USA	Research Related to Deafness and Communication Disorders	000	2	12/24/2020	NON-COMPETING CONTINUATION	$45,520
														Subtotal = $46,036

Issue Date FY: 2019 ( Subtotal = $45,016 )
2019	2019	UNIVERSITY OF MIAMI	1320 S DIXIE HWY STE 650	CORAL GABLES	FL	33146	MIAMI-DADE	USA	Research Related to Deafness and Communication Disorders	001	1	8/19/2019	NEW	$0
2019	2019	UNIVERSITY OF MIAMI	1320 S DIXIE HWY STE 650	CORAL GABLES	FL	33146	MIAMI-DADE	USA	Research Related to Deafness and Communication Disorders	000	1	8/19/2019	NEW	$45,016
														Subtotal = $45,016

Grand Total All Awards = $115,041

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Efficacy and Mechanisms of Mild Therapeutic Hypothermia for Hearing Preservation from NIHL

Award Number: F31DC018212

ORGANIZATION: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 01/09/2020

PERIOD OF PERFORMANCE END DATE: 11/08/2022

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