title: Cytomegalovirus (CMV) Infection Causes Degeneration of Cochlear Vasculature and Hearing Loss in a Mouse Model.
abstract: Cytomegalovirus (CMV) infection is one of the most common causes of congenital hearing loss in children. We have used a murine model of CMV infection to reveal functional and structural cochlear pathogenesis. The cerebral cortex of Balb/c mice (Mus musculus) was inoculated with 2000 pfu (plaque forming units) of murine CMV on postnatal day 3. At 6 weeks of age, cochlear function was monitored using auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) measures. Histological assessment of cochlear vasculature using a corrosion cast technique was made at 8 weeks. Vascular casts of mCMV-damaged cochleas, and those of untreated control animals, were examined using scanning electron microscopy. We find very large variations in the degree of vascular damage in animals given identical viral injections (2000 pfu). The primary lesion caused by CMV infection is to the stria vascularis and to the adjacent spiral limbus capillary network. Capillary beds of the spiral ligament are generally less affected. The initial vascular damage is found in the mid-apical turn and appears to progress to more basal cochlear regions. After viral migration to the inner ear, the stria vascularis is the primary affected structure. We suggest that initial auditory threshold losses may relate to the poor development or maintenance of the endocochlear potential caused by strial dysfunction. Our increased understanding of the pathogenesis of CMV-related hearing loss is important for defining methods for early detection and treatment.
authors.affiliation: Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada.|Auditory Science Laboratory, Neuroscience and Mental Health Program, The Hospital for Sick Children, Toronto, ON, Canada.
authors.forename: Mattia
authors.initials: M
authors.lastname: Carraro
authors.affiliation: Department of Communication Sciences and Disorders, University of Utah, Salt Lake City, UT, USA.
authors.forename: Ali
authors.initials: A
authors.lastname: Almishaal
authors.affiliation: Department of Surgery, University of Utah, Salt Lake City, UT, USA.
authors.forename: Elaine
authors.initials: E
authors.lastname: Hillas
authors.affiliation: Department of Surgery, University of Utah, Salt Lake City, UT, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Firpo
authors.affiliation: Department of Surgery, University of Utah, Salt Lake City, UT, USA.|Department of Otolaryngology, University of Utah, Salt Lake City, UT, USA.
authors.forename: Albert
authors.initials: A
authors.lastname: Park
authors.affiliation: Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada. rvh@sickkids.ca.|Auditory Science Laboratory, Neuroscience and Mental Health Program, The Hospital for Sick Children, Toronto, ON, Canada. rvh@sickkids.ca.|Department of Otolaryngology, Head and Neck Surgery, University of Toronto, Toronto, ON, Canada. rvh@sickkids.ca.
authors.forename: Robert V
authors.initials: RV
authors.lastname: Harrison
mesh_terms: D000818:Animals; D002196:Capillaries / Q000473:pathology; D003051:Cochlea / Q000098:blood supply* / Q000503:physiopathology / Q000648:ultrastructure; D016319:Corrosion Casting; D003586:Cytomegalovirus Infections / Q000150:complications / Q000473:pathology*; D034381:Hearing Loss / Q000209:etiology* / Q000473:pathology; D008807:Mice, Inbred BALB C; D008855:Microscopy, Electron, Scanning
keywords: congenital hearing loss; corrosion casting; endocochlear potential; endolymphatic potential; scanning electron microscopy; sensorineural deafness; spiral ligament; spiral limbus; stria vascularis