Spiral ganglion loss outpaces inner hair cell loss in endolymphatic hydrops

Abstract

Objectives/Hypothesis: Neuronal toxicity is thought to be important in Meniere's disease and experimental endolymphatic hydrops (ELH). This study quantifies the relationship between neuronal degeneration and hair cell degeneration in ELH to evaluate the hypothesis that a primary neural insult would yield greater loss in the spiral ganglion than at the inner hair cell level.Study Design: Following induction and histopathologic confirmation of endolymphatic hydrops in guinea pigs, the degree of hydrops, spiral ganglion loss, and hair cell degeneration were quantified and compared.Methods: Guinea pigs with surgically induced unilateral hydrops were sacrificed and their cochleas preserved. Hydrops severity and spiral ganglion density were quantified using automated methods. Hair cells were counted manually. Values were normalized against the contralateral ear to create loss indexes.Results: Inner hair cell (IHC) loss at the apex is significantly lower than corresponding neuronal loss. IHC loss at the base is also lower than neuron loss, although not significantly. Regression analysis shows a significant, positive correlation between neuron loss severity and IHC loss severity at the apex, but not at the base. There is no correlation between hydrops severity and inner hair cell loss.Conclusions: By confirming that spiral ganglion loss is more severe than hair cell loss, and that hair cell loss appears to worsen with neuronal degeneration, this study supports the theory that neuronal toxicity is the primary insult in ELH-related disorders, such as Meniere's disease, and may provide the basis for designing treatment strategies.

A Genetic Murine Model of Endolymphatic Hydrops: The Phex Mouse

“…Both the Hyp-Duk/Y and guinea pig surgical models support the theory of ELH progression from the cochlear apex to the cochlear basal turn. The animal models also agree that SGN degeneration progresses in an orientation similar to ELH and precedes hair cell loss [24,25]. Human temporal bone specimens in patients with MD recapitulate these experimental findings [44-46].…”

“…Through the guinea pig model, the sequelae of neural damage and SNHL have begun to take shape. Spiral ganglion neurons (SGNs) degenerate in an apical to basal pattern [24], which precedes the degeneration of inner hair cells [25] and ultimately results in a reduced cochlear nerve diameter [26]. The relationship between the degree of ELH and the degree of SNHL was correlated in humans [27] and recapitulated in the guinea pig model [28, 26].…”

Oral Steroid Treatment for Hearing Improvement in Ménière’s Disease and Endolymphatic Hydrops

“…It may be that the initial site leading to distension of Reissner's membrane is some type of neuronal insult (45). The apical ganglion cells exhibit damage before, and to a greater degree, than basal ganglion cells.…”

Functional Variants inNOS1andNOS2AAre Not Associated with Progressive Hearing Loss in Ménière's Disease in a European Caucasian Population

“…This relationship may be related to transformation of NO to NO À , a highly reactive free radical that can conjugate with other free radicals to become cytotoxic at high concentrations or under oxidative conditions. Interestingly, both NOS1 and NOS2A are upregulated in SGNs in a model of ELH, suggesting that variants of these genes may be related to the neurotoxicity and apoptosis of SGNs in MD (Michel et al, 2000;Anne et al, 2007;Momin et al, 2010).…”

“…The hearing loss usually affects the low frequencies first, and in an animal model of endolymphatic hydrops (ELH), it is associated with loss of spiral ganglion neurons (SGNs), suggesting that neuronal apoptosis beginning at the apex may be the primary damage in MD (Merchant et al, 2005;Momin et al, 2010). Relevant to this pathophysiology is the observation that chronic stimulation of glutamate receptors of nerve afferents causes an N-methyl-d-aspartate (NMDA)-mediated toxicity, which leads to oxidative stress in SGNs (Anne et al, 2007;Bixenstine et al, 2008).…”