Evidence map›Paper›PMID 31653916›Full record

ArticleScientific reports2019

Protection from noise-induced cochlear synaptopathy by virally mediated overexpression of NT3.

Ken Hashimoto, Tyler T Hickman, Jun Suzuki, Lingchao Ji, David C Kohrman, Gabriel Corfas, M Charles Liberman

Registry-linked trialOpen access · goldAbstract read
In one paragraph

Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06729632 (Non-Invasive System to Deliver Therapeutic Hypothermia for Protection Against Noise-Induced Hearing Loss), which is not on this map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
3.3field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT06729632 narecruitingnot on this mapstarted 2024, after this paper: background citation

Non-Invasive System to Deliver Therapeutic Hypothermia for Protection Against Noise-Induced Hearing Loss

TypeinterventionalSponsorRestorear Devices LLCRan2024 to 2027Enrolled116ConditionsNoise Exposure, Noise-induced Hearing Loss, Noise, Adverse EffectArmsCold pack-delivered mild therapeutic hypothermia
3 · Its place in the literature

Who cites it

32 citing papers in PubMed, 49 citations in OpenAlex.

  1. Article
  2. Review
  3. Optimizing Factors in Murine Whole-Organ Cochlea Culture.International journal of molecular sciences · 2025
    Article
  4. Article
  5. Review
  6. Auditory hair cells and spiral ganglion neurons regenerate synapses with refined release properties in vitro.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  7. Article
  8. Eurycomanone fromJournal of clinical biochemistry and nutrition · 2024
    Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Engineering olivocochlear inhibition to reduce acoustic trauma.Molecular therapy. Methods & clinical development · 2023
    Article
  16. Article
  17. Article
  18. Article
  19. Current Advances in Adeno-Associated Virus-Mediated Gene Therapy to Prevent Acquired Hearing Loss.Journal of the Association for Research in Otolaryngology : JARO · 2022
    Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 2 countries.

Ken HashimotoDepartment of Otolaryngology-Head and Neck Surgery, Harvard Medical School, Boston, MA, USA.
Tyler T HickmanDepartment of Otolaryngology-Head and Neck Surgery, Harvard Medical School, Boston, MA, USA. Tyler_Hickman@meei.harvard.edu.ORCID http://orcid.org/0000-0003-2623-3251
Jun SuzukiDepartment of Otolaryngology-Head and Neck Surgery, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-9164-6389
Lingchao JiKresge Hearing Research Institute, University of Michigan, Ann Arbor, MI, USA.
David C KohrmanKresge Hearing Research Institute, University of Michigan, Ann Arbor, MI, USA.
Gabriel CorfasKresge Hearing Research Institute, University of Michigan, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0001-5412-9473
M Charles LibermanDepartment of Otolaryngology-Head and Neck Surgery, Harvard Medical School, Boston, MA, USA.
Massachusetts Eye and Ear Infirmary · USUniversity of Michigan · US

Funding

SINGLE-NEURON MARKING IN THE STUDY OF ABNORMAL COCHLEASR01DC000188 · NIDCD · MASSACHUSETTS EYE AND EAR INFIRMARY · PI Gabriel Corfas, M. Charles Liberman · 1989 to 2026
$15.1M
Trophic Interactions in the Developing and Adult Inner EarR01DC004820 · NIDCD · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CORFAS, GABRIEL · 2002 to 2019
$6.2M
NIDCD NIH HHS R01 DC000188NIDCD NIH HHS R01 DC004820
6 · The paper itself

Abstract

Noise exposures causing only transient threshold shifts can destroy auditory-nerve synapses without damaging hair cells. Here, we asked whether virally mediated neurotrophin3 (NT3) overexpression can repair this damage. CBA/CaJ mice at 6 wks were injected unilaterally with adeno-associated virus (AAV) containing either NT3 or GFP genes, via the posterior semicircular canal, 3 wks prior to, or 5 hrs after, noise exposure. Controls included exposed animals receiving vehicle only, and unexposed animals receiving virus. Thresholds were measured 2 wks post-exposure, just before cochleas were harvested for histological analysis. In separate virus-injected animals, unexposed cochleas were extracted for qRT-PCR. The GFP reporter showed that inner hair cells (IHCs) were transfected throughout the cochlea, and outer hair cells mainly in the apex. qRT-PCR showed 4- to 10-fold overexpression of NT3 from 1-21 days post-injection, and 1.7-fold overexpression at 40 days. AAV-NT3 delivered prior to noise exposure produced a dose-dependent reduction of synaptopathy, with nearly complete rescue at some cochlear locations. In unexposed ears, NT3 overexpression did not affect thresholds, however GFP overexpression caused IHC loss. In exposed ears, NT3 overexpression increased permanent threshold shifts. Thus, although NT3 overexpression can minimize noise-induced synaptic damage, the forced overexpression may be harmful to hair cells themselves during cochlear overstimulation.

Indexed as

NoiseAnimalsAuditory ThresholdCochleaDependovirusEvoked Potentials, Auditory, Brain StemGreen Fluorescent ProteinsHair Cells, Auditory, InnerHair Cells, Auditory, OuterMaleMice, Inbred C57BLMice, Inbred CBANeurotrophin 3Otoacoustic Emissions, SpontaneousRNA, MessengerSynapsesGreen Fluorescent ProteinsNeurotrophin 3RNA, Messenger

Identifiers

PMID31653916
PMCPMC6814859
OpenAlexW2981735461

What OpenQuestion holds

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LicenceCC BY
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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.