Trauma‐specific insults to the cochlear nucleus in the rat

Abstract

The effect of acoustic overstimulation on the neuronal number of the cochlear nucleus (CN) was investigated by using unbiased stereological methods in rats. We found that, after 9 weeks of recovery, neurons in the anteroventral cochlear nucleus (AVCN) degenerated, whereas those in the posteroventral and dorsal cochlear nuclei (PVCN and DCN) were preserved. The noise trauma induced near complete loss of the outer hair cells throughout the cochlea, and the inner hair cells were preserved only in the more apical regions. This pattern of selective loss of AVCN neurons in this study was different from trauma induced by auditory deafferentation by mechanical compression of auditory neurons. In contrast to noise trauma, mechanical compression caused loss of neurons in the PVCN and DCN. After 5 weeks of recovery from mechanical compression, there was no loss of inner or outer hair cells. These findings indicate that auditory deprivation, induced by different experimental manipulations, can have strikingly different consequences for the central auditory system. We hypothesized that AVCN neuronal death was induced by excitotoxic mechanisms via AMPA-type glutamate receptors and that excitatory neuronal circuits developed after acoustic overstimulation protected the PVCN and DCN against neuronal death. The results of the present study demonstrate that hearing loss from different etiologies will cause different patterns of neuronal degeneration in the CN. These findings are important for enhancing the performance of cochlear implants and auditory brainstem implants, because diverse types of hearing loss can selectively affect neuronal degeneration of the CN.

Cells transplanted onto the surface of the glial scar reveal hidden potential for functional neural regeneration

“…Animal experiments were conducted in accordance with the Guidelines for Animal Experiments at Kyoto University. Exposing of the auditory nerve of male Sprague-Dawley rats (P7-8 wk) was performed as previously reported (7,8,10,11). For compression, a nerve hook (tip diameter: 0.15 mm, No.…”

“…Temporal bones were obtained and processed as previously reported (7,8,10,11). The section angle was chosen so that the auditory nerve trunk, PVCN, and DCN were simultaneously included in one section as fully as possible by reference to figures 1 and 2 in Hackney et al (56).…”

“…In our experimental model, the posteroventral cochlear nucleus (PVCN) is affected most, the dorsal cochlear nucleus (DCN) less, and the anteroventral cochlear nucleus (AVCN) was not affected (8). Hence, to most clearly evaluate how the transplanted cells reinnervate cochlear nucleus cells, we chose to evaluate the PVCN.…”

“…We developed an in vivo model of the chronic gliotic environment in clinical patients by compressing the rat auditory nerve without breaching the fluid spaces that contain the sensory structures inside the cochlea (7)(8)(9)(10). In this model, spiral ganglion cells (the auditory neurons) degenerate selectively, but hair cells are preserved both morphologically and functionally (7,8,10,11). We then waited 5 wk before cell transplantation to allow the formation of a glial scar with the progressive degeneration of auditory neurons.…”

Cochlear implantation for chronic electrical stimulation in the mouse

“…With the exception of the congenitally Deaf White Cat (i.e. Hartmann et al, 1997;Ryugo et al, 2010;Klinke et al, 1999), these animals are typically deafened by experimental intervention, such as administration of ototoxic drugs (Shepherd and Martin, 1995;Fallon et al, 2009;Ryugo et al, 2010;Leake et al, 1999), or loud noise exposure (Eggermont and Komiya, 2000;Robertson and Anderson, 1994;Sekiya et al, 2012) to produce a sensorineural hearing loss. Although relevant to clinical populations, these deafness models do not encompass the numerous genetic causes of deafness which are highly prevalent in clinical populations (Morzaria et al, 2004).…”