PMID- 32116980
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20221202
IS  - 1664-2295 (Print)
IS  - 1664-2295 (Electronic)
IS  - 1664-2295 (Linking)
VI  - 10
DP  - 2019
TI  - Intracochlear Perfusion of Tumor Necrosis Factor-Alpha Induces Sensorineural 
      Hearing Loss and Synaptic Degeneration in Guinea Pigs.
PG  - 1353
LID - 10.3389/fneur.2019.01353 [doi]
LID - 1353
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine that plays a 
      prominent role in the nervous system, mediating a range of physiologic and 
      pathologic functions. In the auditory system, elevated levels of TNF-alpha have been 
      implicated in several types of sensorineural hearing loss, including 
      sensorineural hearing loss induced by vestibular schwannoma, a potentially fatal 
      intracranial tumor that originates from the eighth cranial nerve; however, the 
      mechanisms underlying the tumor's deleterious effects on hearing are not 
      well-understood. Here, we investigated the effect of acute elevations of TNF-alpha in 
      the inner ear on cochlear function and morphology by perfusing the cochlea with 
      TNF-alpha in vivo in guinea pigs. TNF-alpha perfusion did not significantly change 
      thresholds for compound action potential (CAP) responses, which reflect cochlear 
      nerve activity, or distortion product otoacoustic emissions, which reflect outer 
      hair cell integrity. However, intracochlear TNF-alpha perfusion reduced CAP 
      amplitudes and increased the number of inner hair cell synapses without paired 
      post-synaptic terminals, suggesting a pattern of synaptic degeneration that 
      resembles that observed in primary cochlear neuropathy. Additionally, etanercept, 
      a TNF-alpha blocker, protected against TNF-alpha-induced synaptopathy when administered 
      systemically prior to intracochlear TNF-alpha perfusion. Findings motivate further 
      investigation into the harmful effects of chronically elevated intracochlear 
      levels of TNF-alpha, and the potential for etanercept to counter these effects.
CI  - Copyright (c) 2020 Katsumi, Sahin, Lewis, Iyer, Landegger and Stankovic.
FAU - Katsumi, Sachiyo
AU  - Katsumi S
AD  - Eaton Peabody Laboratories, Department of Otolaryngology-Head and Neck Surgery, 
      Massachusetts Eye and Ear, Boston, MA, United States.
AD  - Department of Otolaryngology-Head and Neck Surgery, Harvard Medical School, 
      Boston, MA, United States.
FAU - Sahin, Mehmet I
AU  - Sahin MI
AD  - Eaton Peabody Laboratories, Department of Otolaryngology-Head and Neck Surgery, 
      Massachusetts Eye and Ear, Boston, MA, United States.
AD  - Department of Otolaryngology-Head and Neck Surgery, Harvard Medical School, 
      Boston, MA, United States.
FAU - Lewis, Rebecca M
AU  - Lewis RM
AD  - Eaton Peabody Laboratories, Department of Otolaryngology-Head and Neck Surgery, 
      Massachusetts Eye and Ear, Boston, MA, United States.
AD  - Department of Otolaryngology-Head and Neck Surgery, Harvard Medical School, 
      Boston, MA, United States.
FAU - Iyer, Janani S
AU  - Iyer JS
AD  - Eaton Peabody Laboratories, Department of Otolaryngology-Head and Neck Surgery, 
      Massachusetts Eye and Ear, Boston, MA, United States.
AD  - Department of Otolaryngology-Head and Neck Surgery, Harvard Medical School, 
      Boston, MA, United States.
AD  - Program in Speech and Hearing Bioscience and Technology, Harvard Medical School, 
      Boston, MA, United States.
FAU - Landegger, Lukas D
AU  - Landegger LD
AD  - Eaton Peabody Laboratories, Department of Otolaryngology-Head and Neck Surgery, 
      Massachusetts Eye and Ear, Boston, MA, United States.
AD  - Department of Otolaryngology-Head and Neck Surgery, Harvard Medical School, 
      Boston, MA, United States.
FAU - Stankovic, Konstantina M
AU  - Stankovic KM
AD  - Eaton Peabody Laboratories, Department of Otolaryngology-Head and Neck Surgery, 
      Massachusetts Eye and Ear, Boston, MA, United States.
AD  - Department of Otolaryngology-Head and Neck Surgery, Harvard Medical School, 
      Boston, MA, United States.
AD  - Program in Speech and Hearing Bioscience and Technology, Harvard Medical School, 
      Boston, MA, United States.
AD  - Harvard Program in Therapeutic Science, Harvard Medical School, Boston, MA, 
      United States.
LA  - eng
GR  - R01 DC015824/DC/NIDCD NIH HHS/United States
PT  - Journal Article
DEP - 20200210
PL  - Switzerland
TA  - Front Neurol
JT  - Frontiers in neurology
JID - 101546899
PMC - PMC7025643
OTO - NOTNLM
OT  - cochlear synaptopathy
OT  - sensorineural hearing loss
OT  - tumor necrosis factor-alpha
OT  - unpaired (orphaned) ribbons
OT  - vestibular schwannoma
EDAT- 2020/03/03 06:00
MHDA- 2020/03/03 06:01
PMCR- 2020/02/10
CRDT- 2020/03/03 06:00
PHST- 2019/08/09 00:00 [received]
PHST- 2019/12/09 00:00 [accepted]
PHST- 2020/03/03 06:00 [entrez]
PHST- 2020/03/03 06:00 [pubmed]
PHST- 2020/03/03 06:01 [medline]
PHST- 2020/02/10 00:00 [pmc-release]
AID - 10.3389/fneur.2019.01353 [doi]
PST - epublish
SO  - Front Neurol. 2020 Feb 10;10:1353. doi: 10.3389/fneur.2019.01353. eCollection 
      2019.