Time course of efferent fiber and spiral ganglion cell degeneration following complete hair cell loss in the chinchilla

AbstractSpiral ganglion neurons (SGNs) relay auditory information from cochlear hair cells to the central nervous system. After hair cells are destroyed by aminoglycoside antibiotics, SGNs gradually die. However, the reasons for this cochlear neurodegeneration are unclear. We used microarray gene expression profiling to assess transcriptomic changes in the spiral ganglia of kanamycin-deafened and age-matched control rats and found that many of the genes upregulated after deafening are associated with immune/inflammatory responses. In support of this, we observed increased numbers of macrophages in the spiral ganglion of deafened rats. We also found, via CD68 immunoreactivity, an increase in activated macrophages after deafening. An increase in CD68-associated nuclei was observed by postnatal day 23, a time before significant SGN degeneration is observed. Finally, we show that the immunosuppressive drugs dexamethasone and ibuprofen, as well as the NAD salvage pathway activator P7C3, provide at least some neuroprotection post-deafening. Ibuprofen and dexamethasone also decreased the degree of macrophage activation. These results suggest that activated macrophages specifically, and perhaps a more general neuroinflammatory response, are actively contributing to SGN degeneration after hair cell loss.

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Electrocochleographic Changes in Endolymphatic Hydrops Induced by Type II Collagen Immunization through the Stylomastoid Foramen

Annals of Otology Rhinology & Laryngology ◽

10.1177/000348948909800712 ◽

1989 ◽

Vol 98 (7) ◽

pp. 556-562 ◽

Cited By ~ 6

Author(s):

Toru Ohashi ◽

Koichi Tomoda ◽

Nobuo Yoshie

Keyword(s):

Ganglion Cell ◽

Guinea Pigs ◽

Endolymphatic Hydrops ◽

Spiral Ganglion ◽

Type Ii Collagen ◽

Ménière’S Disease ◽

Type Ii ◽

Cell Degeneration ◽

Stylomastoid Foramen ◽

Spiral Ganglion Cell

Changes in action potential (AP) and summating potential (SP) were investigated in guinea pigs immunized with type II collagen through the stylomastoid foramen. Endolymphatic hydrops could be induced in four of 11 guinea pigs. The striking feature of the electrocochleographic waveform in guinea pigs with endolymphatic hydrops was the negative SP recording in response to high frequency tone bursts. Furthermore, abnormal changes in AP were observed in three of four hydropic guinea pigs. Morphologic study of the cochleas in these three guinea pigs with light microscopy revealed spiral ganglion cell degeneration in addition to endolymphatic hydrops and almost normal sensory hair cells. These results suggest that guinea pigs with hydrops as produced by our procedure can serve as a useful model of Meniere's disease, that autoimmune response may play an important role in the etiopathogenesis of Meniere's disease, and that spiral ganglion cell degeneration together with endolymphatic hydrops seems to contribute to abnormal changes in AP.

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