Changes in the cochlear vasculature and vascular endothelial growth factor and its receptors in the aging c57 mouse cochlea.

David Clinkard, Hosam Amoodi, Thileep Kandasamy, Amandeep S Grewal, Stephen Chen, Wei Qian, Joseph M Chen, Robert V Harrison, Vincent Y W Lin
Author Information
  1. David Clinkard: Sunnybrook Health Sciences Centre, Otolaryngology/Head & Neck Surgery, Toronto, Canada M4N 3M5.

Abstract

Introduction. Previous work has shown a strong association between alterations in cochlear vasculature, aging, and the development of presbycusis. The important role of vascular endothelial growth factor (VEGF) and its receptors Flt-1 and Flk-1 in angiogenesis suggests a potential role for involvement in this process. The aim of this study was to characterize vascular structure and VEGF and its' receptors in young and old C57 Mice. Methods. Young (4 weeks, n = 14) and aged (32-36 weeks, n = 14) C57BL/6 mice were used. Hearing was evaluated using auditory brainstem response. Cochleas were characterized with qRT-PCR, immunohistochemistry, and gross histological quantification. Results. Old C57 mice demonstrated significantly decreased strial area, blood vessel number, luminal size, and luminal area normalized to strial area (vascularity). qRT-PCR showed a significant upregulation of Flt-1, a VEGF receptor, in older animals. No differences were found in VEGF-A or Flk-1. Immunohistochemistry did not show any differences in staining intensity or area with age or cochlear turn location. Conclusion. The marked deafness of aged C57 mice could be in part meditated by loss of vascular development and alterations in VEGF signaling.

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Word Cloud

Created with Highcharts 10.0.0vascularVEGFareacochlearreceptorsC57micealterationsvasculatureagingdevelopmentroleendothelialgrowthfactorFlt-1Flk-1weeksn=14agedqRT-PCRstrialluminaldifferencesIntroductionPreviousworkshownstrongassociationpresbycusisimportantangiogenesissuggestspotentialinvolvementprocessaimstudycharacterizestructureits'youngoldMiceMethodsYoung432-36C57BL/6usedHearingevaluatedusingauditorybrainstemresponseCochleascharacterizedimmunohistochemistrygrosshistologicalquantificationResultsOlddemonstratedsignificantlydecreasedbloodvesselnumbersizenormalizedvascularityshowedsignificantupregulationreceptorolderanimalsfoundVEGF-AImmunohistochemistryshowstainingintensityageturnlocationConclusionmarkeddeafnesspartmeditatedlosssignalingChangesc57mousecochlea

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