The Micro-Vasculature of the Cochlea: Studies in Animal Models of Sensorineural Hearing Loss

This thesis concerns the role of cochlear microvasculature in normal hearing function and in pathological conditions that result in hearing loss. In animal models we have investigated two major types of sensorineural hearing loss where degeneration of the stria vascularis has been implicated, namely presbyacusis and hearing loss associated with cytomegalovirus (CMV) infection. The former eventual affects all aging humans; the latter is a common etiology for congenital hearing loss in infants. The focus of experimental work is on the capillary networks of the cochlea. We chose to use corrosion cast techniques to visualize and quantify capillary vessel parameters. For the small and delicate cochleas of our mouse models, this required extensive technical improvements to corrosion casting methodology. These innovations proved successful. Three experimental animal model studies were made. The first involved analysis, and modeling of strial feeding arterioles in normal subject. The hypothesis posed was that the highly convoluted structure of these vessels acts to dampen cardiovascular pulsations within the cochlea and thereby prevent self-stimulation by such biological noise. The results from this study support the hypothesis. In our murine models of presbyacusis and of CMV infection we correlated loss of auditory thresholds measured with ABR methods, with degenerative changes to cochlear microvasculature. In mice with age-related, high frequency hearing loss, we report significant vascular degeneration of stria vascularis in basal (high frequency) cochlear areas compared to more apical regions. After CMV infection in newborn mice, we observed at 6 weeks a wide range of auditory threshold changes. At 8 weeks post-infection, the cochleas had suffered a wide range of vascular damage. The most vulnerable structure was stria vascularis in the mid-apical cochlear turn. Our novel finding that vascular damage is the primary lesion after CMV infection is consistent with some clinical characteristics of this hearing loss type in infants.Ph.D