gms | German Medical Science

81. Jahresversammlung der Deutschen Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie e. V.

Deutsche Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie e. V.

12.05. - 16.05.2010, Wiesbaden

TNFα compromises the inner ear microcirculation in a sphingosine kinase 1/sphingosine-1-phosphate dependent manner – a novel mechanism for sudden hearing loss (SHL)

Meeting Abstract

  • corresponding author Elias Scherer - Hals-Nasen-Ohrenklinik und Poliklinik, München, Deutschland
  • Jingli Yang - Department of Physiology, University of Toronto, Canada
  • Karolina Ivanov - Department of Physiology, University of Toronto, Canada
  • Christian David Diehl - Department of Physiology, University of Toronto, Canada
  • Katrin Reimann - Department of Anatomy and Physiology, Kansas State University, Manhattan, USA
  • Philine Wangemann - Department of Anatomy and Physiology, Kansas State University, Manhattan, USA
  • Martin Canis - Walter Brendel Centre of Experimental Medicine, Ludwig-Maximilians-Universität München, Deutschland
  • Sebastian Strieth - Walter Brendel Centre of Experimental Medicine, Ludwig-Maximilians-Universität München, Deutschland
  • Julia Voigtlaender-Bolz - Department of Physiology, University of Toronto, Canada
  • Steffen-Sebastian Bolz - Department of Physiology, University of Toronto, Canada

Deutsche Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie. 81. Jahresversammlung der Deutschen Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie. Wiesbaden, 12.-16.05.2010. Düsseldorf: German Medical Science GMS Publishing House; 2010. Doc10hnod421

DOI: 10.3205/10hnod421, URN: urn:nbn:de:0183-10hnod4218

Veröffentlicht: 22. April 2010

© 2010 Scherer et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

This study establishes a link between inflammation and inner ear vascular dysfunction. Recovery of auditory function in sudden hearing loss (SHL) patients treated with a TNFα inhibitor were consistent with a vascular origin. We investigated the inner ear microcirculation using (1) an in vitro model of the spiral modiolar artery (SMA), the end artery feeding the inner ear, (2) intra vital microscopy of stria vascularis perfusion, and (3) in vitro measurement of cochlear lateral wall capillary constriction. We demonstrate that in all parts of the cochlear microcirculation (SMA, stria vascularis and cochlear lateral wall capillaries), TNFα induces a proconstrictive state via activation of sphingosine-1-phosphate (S1P). Analysis of the molecular signalling pathway identified the phosphorylation of sphingosine kinase 1 (the S1P generating enzyme activated by TNFα) as a new therapeutic target for SHL. We conclude that any pathology linked to the release of TNFα has the potential to reduce cochlear blood flow and cause SHL. The present study integrates SHL into the family of cardiovascular pathologies, with immediate implications related to risk stratification, diagnosis and treatment.

Supported by: CIHR-MOP-84402, CFI-11810, ORF-11810, CSN, KRICRFTUM-8758155, HSFO-NI, HSFO-CI, SFUT, Boehringer Ingelheim, DAAD, NIH-R01-DC04280.