Patterns of Neurodegeneration in Human Audition

Research of hearing loss in the human imposes a set of distinct difficulties for the researcher as influential variations in genetic, biochemical, vascular, environmental and even nutritional conditions cannot easily be accounted for. Histologically , research conducted with human tissue also poses very unique difficulties as structural preservation and antigenicity are critically dependent on an expeditious fixation. Sensorineural deafness represents all forms of deafness which involve the sensory cells of the organ of Corti as well as the auditory central and peripheral nerve-fiber pathways. Our concerns include three general types of sensorineural hearing loss in the human auditory system: hearing loss from acute to chronic noise-induced trauma, from early presbycusis to the aging cochlea, and from congenital to late-onset, genetic variations. The present study will examine the morphological manifestations of hearing loss in four investigations using immunohistochemical methods, light, scanning and electron microscopy. In the first study on noise-induced hearing loss, we will conduct an ultrastructural study on a organ of Corti exposed to an explosive blast. A second study on High Tone Hearing Loss will conduct a morphological study on the patterns of degeneration found in five temporal bones which are to be correlated with audiograms. Degeneration patterns of sensorineural deafness in central auditory structures will also be carefully examined in the human brainstem of an individual with bilateral cochlear implants, one of which restored full sensation of sound and one which only achieved minimal benefits. Our last study will involve an immunohistochemical investigation into the presence and distribution patterns of several neurotransmitters within the cochlea including: Secretoneurin, Alpha 9 as well as co-localization patterns of GABA and ChAT. Findings are to be demonstrated and discussed.

Hair cells in the cochlea are secondary sensory cells and therefore unable to generate an action potential. They communicate their responses to the central nervous system by making afferent contacts to ganglion cells in the cochlea that are able to spike. These spiral ganglion cells are located in the central part of the cochlear spiral and send their peripheral processes to the hair cells. A degeneration of theses hair cells due to ototoxic drugs (e.g. some antibiotics in high doses) noise trauma or hereditary mutations leads to hearing loss or deafness. Cochlear implants are able to bypass this lost sensory cells and directly stimulate the auditory nerve. The introduction of this electrical stimulation in treating profound sensorineural hearing loss has added new significance to the histopathology of various etiologies of deafness. At present very little is known about degeneration patterns in human. This project provides new insights into the human cochlea and outlines differences to current animal models. Inner ears from patients with genetic syndromes such as Alport-, Usher- and Pendred Syndrome and Trisomy 21 were studies in this project. A new tomographic method using synchrotron radiation was first time tested with a human cochlea with implanted electrode and offers high resolution 3D-data not available before. A cochlea with implanted electrode showed intense new bone formation, fibrosis und degeneration of neurons and nerve fibers, in both peripheral and central auditory pathways. More than 50 years after losing hearing due to noise trauma we were able to find plenty of neurons and central processes in the inner ear of a patient. This robust survival differs from rodent animal models. Microanatomical differences were studied with surgical human tissue and electron microscopy. In collaboration with the Kresge Hearing Institute in Ann Arbor Michigan, USA we analyzed the degeneration pattern following ototoxic drug application with focus on the peripheral processes in a guinea pig model. Nerve growth factors, electrical stimulation or a combination of both may rescue spiral ganglion cells from deafferentation-induced death and promote regrowth of afferent nerve fibres. Regrown fibres directed into the region of the sensory epithelium, as well as into the fluid filled compartments may have significant implications for a closer integration of cochlear implants with the auditory nerve, increase specifity and lower thresholds of electrostimulation of the auditory nerve. We showed that with the local application of nerve growth factors afferent fibres were able to regrow and spiral ganglion neuron densities even increased, degeneration of the efferent nerve fibre system could not be prevented. A scaffold of (fibrous) tissue seems to be necessary to guide these fibres towards the electrode to promote this regrowth.