A possible molecular mechanism of hearing loss during cerebral ischemia in mice

Pradip Kumar Kamat, Anuradha Kalani, Naira Metreveli, Suresh C. Tyagi, Neetu Tyagi

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Ischemic brain stroke is a leading cause of disability and includes hearing loss. Clinical reports have also suggested that there is hearing loss in stroke patients but the mechanism was not determined. Therefore, we hypothesized that hearing loss after cerebral ischemia may be associated with changes to the synapse, gap junction, and sodium channel (NaC) proteins. Ischemia– reperfusion injury was induced in wild-type mice (I/R group). The lesion volume was determined by 2,3,5-triphenyltetrazolium chloride (TTC) staining of the brain sections. BBB disruption was confirmed by Evans blue staining and leakage of bovine serum albumin labeled with fluorescein isothiocyanate (BSA-FITC).Wefound that brain edema, infarct size, and permeability were increased in ischemic mice as compared with the sham-operated group. Caspase-3, caspase-9, and TUNEL-positive cells were increased in I/R mice, indicating neuronal apoptosis. Moreover, there were increased expressions of matrix metalloprotease’s (MMP-2, -3, -9, and -13), interleukin (IL)-6, and decreased expressions of tight junction proteins (TJP) in the I/R group, as compared with the sham group, which signifies inflammation and BBB disruption. We also observed decreased levels of post-synaptic density protein-95 (PSD-95), synapseassociated protein 97 (SAP-97), connexin-43, NaC-α, and NaC-β, and increased expression of connexin-45, whereas no substantial change was observed in connexin-26 expression in the I/R group. Interestingly, auditory response was reduced in the I/R mice, indicating hearing loss. These data suggest that hearing loss in ischemic mice was primarily due to alterations in connexin, synapses, and NaC channels.

Original languageEnglish (US)
Pages (from-to)505-516
Number of pages12
JournalCanadian Journal of Physiology and Pharmacology
Volume93
Issue number7
DOIs
StatePublished - Mar 11 2015
Externally publishedYes

Keywords

  • Apoptosis
  • Blood–brain barrier
  • Cerebral ischemia
  • Hearing loss
  • Neurotransmission

ASJC Scopus subject areas

  • Physiology
  • Pharmacology
  • Physiology (medical)

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