Sepsis Otopathy: Experimental Sepsis Leads to Significant Hearing Impairment Due to Apoptosis and Glutamate Excitotoxicity in Murine Cochlea

Dis Model Mech. 2013 May;6(3):745-54. doi: 10.1242/dmm.011205. Epub 2013 Feb 14.

Abstract

Hearing loss is frequent in intensive care patients and can be due to several causes. However, sepsis has not been examined as a possible cause. The aim of this study is to assess the influence of experimental sepsis on hearing thresholds and to evaluate pathological changes in the cochlea. The cecal ligation puncture technique was used to induce sepsis in 18 mice. Results were compared with those from 13 sham-operated and 13 untreated control mice. The hearing thresholds of the animals were evaluated with auditory evoked brainstem responses prior to the induction of sepsis and again at the peak of the disease. Immediately after the second measurement, the mice were sacrificed and the inner ears harvested and prepared for further evaluation. The cochleae were examined with light microscopy, electron microscopy and immunohistochemistry for Bax, cleaved caspase-3 and Bcl-2. The mice with sepsis showed a significant hearing loss but not the control groups. Induction of apoptosis could be shown in the supporting cells of the organ of Corti. Furthermore, excitotoxicity could be shown at the basal pole of the inner hair cells. In this murine model, sepsis leads to significant hearing impairment. The physiological alteration could be linked to apoptosis in the supporting cells of the organ of Corti and to a disturbance of the synapses of the inner hair cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Body Temperature / drug effects
  • Body Weight / drug effects
  • Caspase 3 / metabolism
  • Cochlea / enzymology
  • Cochlea / pathology
  • Cochlea / physiopathology
  • Cochlea / ultrastructure
  • Evoked Potentials, Auditory, Brain Stem
  • Glutamic Acid / toxicity*
  • Hair Cells, Auditory, Inner / drug effects
  • Hair Cells, Auditory, Inner / pathology
  • Hair Cells, Auditory, Inner / ultrastructure
  • Hearing Loss / complications*
  • Hearing Loss / pathology*
  • Hearing Loss / physiopathology
  • Immunohistochemistry
  • Ligation
  • Mice
  • Mice, Inbred C57BL
  • Neurotoxins / toxicity*
  • Punctures
  • Sepsis / complications*
  • Sepsis / pathology*
  • Sepsis / physiopathology
  • bcl-2-Associated X Protein / metabolism

Substances

  • Neurotoxins
  • bcl-2-Associated X Protein
  • Glutamic Acid
  • Caspase 3