Loss Of Spiral Ganglion Cells Research Articles

A mouse model with postnatal endolymphatic hydrops and hearing loss

Endolymphatic hydrops (ELH), hearing loss and neuronal degeneration occur together in a variety of clinically significant disorders, including Meniere’s disease (MD). However, the sequence of these pathological changes and their relationship to each other are not well understood. In this regard, an animal model that spontaneously develops these features postnatally would be useful for research purposes. A search for such a model led us to the Phex Hyp-Duk mouse, a mutant allele of the Phex gene causing X-linked hypophosphatemic rickets. The hemizygous male ( Phex Hyp-Duk /Y) was previously reported to exhibit various abnormalities during adulthood, including thickening of bone, ELH and hearing loss. The reported inner-ear phenotype was suggestive of progressive pathology and spontaneous development of ELH postnatally, but not conclusive. The main focuses of this report are to further characterize the inner ear phenotype in Phex Hyp-Duk /Y mice and to test the hypotheses that (a) the Phex Hyp-Duk /Y mouse develops ELH and hearing loss postnatally, and (b) the development of ELH in the Phex Hyp-Duk /Y mouse is associated with obstruction of the endolymphatic duct (ED) due to thickening of the surrounding bone. Auditory brainstem response (ABR) recordings at various times points and histological analysis of representative temporal bones reveal that Phex Hyp-Duk /Y mice typically develop adult onset, asymmetric, progressive hearing loss closely followed by the onset of ELH. ABR and histological data show that functional degeneration precedes structural degeneration. The major degenerative correlate of hearing loss and ELH in the mutants is the primary loss of spiral ganglion cells. Further, Phex Hyp-Duk /Y mice develop ELH without evidence of ED obstruction, supporting the idea that ELH can be induced by a mechanism other than the blockade of longitudinal flow of endolymphatic fluid, and occlusion of ED is not a prerequisite for the development of ELH in patients.

Early Sensorineural Hearing Loss in Ob/Ob Mouse, an Animal Model of Type 2 Diabetes

ObjectivesThere have been many studies on the relationship between diabetes mellitus and presbycusis. Microangiopathy and neuropathy that's caused by chronic hyperglycemia may lead to damage to the inner ear. Several clinical studies on humans and animal studies have been performed to investigate the association between diabetes and hearing loss, however, this relationship is still a matter of debate. We investigated the association of diabetes and sensorineural hearing loss in an animal model of type-2 diabetes and obesity (the ob/ob mouse [OM]).MethodsThe auditory brainstem response (ABR) thresholds were obtained in the OM and the wild type mice (C57BL/6J mice) up to 25 weeks after birth. After the animals were sacrificed, their cochleae were retrieved and then subjected to histopathologic observations.ResultsThe OM exhibited significantly elevated ABR thresholds at 21 weeks of age, yet the C57BL/6J mice exhibited no significant change until 25 weeks of age. On the histological findings, outer hair cell degeneration and loss of spiral ganglion cells were observed in the middle and basal turns of the OM. On the contrary, no degenerative change was observed until 25 weeks of age in the C57BL/6J mice.ConclusionThis study suggests that chronic hyperglycemia and obesity may lead to early sensorineural hearing loss.

The Effect of Organ of Corti Loss on Ganglion Cell Survival in Humans

Severe spiral ganglion cell loss does not necessarily follow loss of hair cells or supporting cells in humans. Despite some publications to the contrary, statements that loss of hair cells and/or supporting cells of the organ of Corti results in a severe loss of spiral ganglion cells in humans still appear in the literature, especially in respect to cochlear implants. This assumption is apparently based on studies in animals or cell culture and not from studies of human temporal bones. Morphological analysis of archival temporal bones with microscopic and statistical analysis of ganglion cell, hair cell, and supporting cell populations was performed in 33 ears with total hearing losses of varying causes and durations of deafness. None of the ears had remaining hair cells. Six ears had had cochlear implants. Ganglion cell counts ranging from 2,889 to 34,299 and the corresponding percentage of remaining ganglion cells based on age-normative data were not significantly related to the duration of hearing loss (r = -0.13 and 0.02, respectively, p > 0.05) or to remaining supporting cell populations (r's from 0.15 to 0.27, p > 0.05). More than half of ears (51.5%) had ganglion cell counts within two standard deviations of age-normative means. Mean ganglion cell counts and percentage of remaining ganglion cells of ears with surviving peripheral processes (dendrites) did not differ significantly from those of ears with no peripheral processes. The loss of hair and supporting cells in the organ of Corti in humans does not necessarily result in as significant a loss of spiral ganglion cells as has been reported animals. In fact, our results suggest that ganglion cell loss may be a primary concomitant loss due to the disease process.

Distribution of Low-Frequency Nerve Fibers in the Auditory Nerve

Low-frequency cochlear fibers are on the outer surface of the auditory nerve adjacent to the vestibular nerve in the distal part of the internal auditory canal. There is a misconception that low-frequency cochlear fibers are in the core of the cochlear nerve and are surrounded by high-frequency fibers. We analyzed temporal bones with a loss of upper spiral ganglion cells caused by different etiologies (n = 6) and traced the corresponding fibers into the distal internal auditory canal. Spiral ganglion cells for each segment (I-IV) of the cochlea were counted, and we defined the location of nerve fibers from the various segments. There was total or near-total degeneration of the upper spiral ganglion cells in these bones. Corresponding low-frequency fibers were on the outer surface of the cochlear nerve adjacent to the vestibular nerve in the distal segment of the internal auditory canal. Low-frequency fibers seem to be located at the periphery of the cochlear nerve. These findings provide one possible explanation for the low-frequency sensorineural hearing loss found in 10% of patients with vestibular nerve schwannomas and may have clinical relevance in the diagnosis of these lesions.

Temporal Bone Histopathologic Abnormalities Associated With Mitochondrial Mutation T7511C

We previously reported a mitochondrial T7511C mutation in the tRNA gene in a Japanese family with nonsyndromic hearing loss (HL). However, the temporal bone histopathology associated with T7511C has not been reported. The aim of the present study is to report histopathologic findings of a temporal bone from a patient in the Japanese family with this mutation. Single case study. A temporal bone was obtained from the right ear of a male subject with progressive HL from 5 years of age and who died at 60 years of age from cerebral infarction. The bone was embedded, sectioned, and stained with hematoxylin-eosin for light microscopic study. Graphic reconstruction of the cochlea was performed using the method described by Schuknecht to determine loss of the stria vascularis and neurosensory elements including hair cells and spiral ganglion neurons. The most significant histopathologic finding was severe loss of spiral ganglion cells in all turns of the cochlea. Severe loss of neuronal filaments in Rosenthal's canal was also observed. The organ of Corti showed scattered loss of inner and outer hair cells in the basal turn. Partial atrophy of the stria vascularis was observed in all turns of the cochlea. Our results suggest that severe loss of spiral ganglion cells was the main cause of sensorineural HL associated with the T7511C mutation.

Synaptic alterations at inner hair cells precede spiral ganglion cell loss in aging C57BL/6J mice

Hearing deficits have often been associated with loss of or damage to receptor hair cells and/or degeneration of spiral ganglion cells. There are, however, some physiological abnormalities that are not reliably attributed to loss of these cells. The afferent synapse between radial fibers of spiral ganglion neurons and inner hair cells (IHCs) emerges as another site that could be involved in transmission abnormalities. We tested the hypothesis that the structure of these afferent terminals would differ between young animals and older animals with significant hearing loss. Afferent endings and their synapses were examined by transmission electron microscopy at approximately 45% distance from the basal end of the cochlea in 2–3 month-old and 8–12 month-old C57BL/6J mice. The number of terminals in older animals was reduced by half compared to younger animals. In contrast, there was no difference in the density of SGCs between the age groups. Older animals featured enlarged terminals and mitochondria and enlarged postsynaptic densities and presynaptic bodies. These morphological changes may be a combination of pathologic, adaptive and compensatory responses to sensory dysfunction. Improved knowledge of these processes is necessary to understand the role of afferent connectivity in dysfunction of the aging cochlea.

Neurotrophe Faktoren der GDNF-Familie und ihre Rezeptoren lassen sich in Spiralganglienzellen hörender, aber auch ertaubter Ratten nachweisen

Recent studies have shown that neurotrophic factors like BDNF, NT-3 and GDNF induce protective effects on spiral ganglion cells after noise- or drug-induced hearing loss. According to these studies it is suggested that deafness leads to a lack of neurotrophic factor or relating receptor expression in spiral ganglion cells, that has to be compensated by local cochlear application of these factors. In the present study we examined the expression pattern of members of the GDNF family (GDNF, Neurturin, Artemin, Persephin) and their relating receptors (Ret, GFRalpha1 - 3) as well as BDNF and trkB on spiral ganglion cells of normal hearing and experimentally deafened rats (10 % neomycine). Indirect immunofluorescence was carried out to determine protein expression of these factors and their receptors 26 days following deafening. Our results demonstrate neurotrophic factor and receptor expression on spiral ganglion cells of normal hearing as well as experimentally deafened animals. Our data indicate that within a period of 26 days after deafening no detectable reduction of the GDNF-family member expression and their receptors was ascertainable on spiral ganglion cells by immunohistochemistry. Thus, a lack of neurotrophic factor expression is unlikely to be the only cause of spiral ganglion cell loss following deafening.

Age-related histopathologic changes in the human cochlea: A temporal bone study

Previous reports on aging of human cochlea included subjects with ear diseases or ototoxic drugs. We studied spiral ganglion cells, hair cells, and lateral wall of cochlea from subjects without ear disease or ototoxic drugs. This study included 39 temporal bones from 24 subjects aged 1 day to 86 years. We assessed standard cytocochleograms, mean loss of fibrocytes in spiral ligament, and areas of stria vascularis. Losses of outer hair cells and fibrocytes were significantly greater in children, adults, and the elderly compared with infants. Spiral ganglion cell loss was significantly greater in adults and elderly compared with infants and children. Areas of stria vascularis of infants were significantly larger than the elderly. Degenerative changes of outer hair cells occur in children but spiral ganglion cells remain the same until around 20 years. Degeneration of stria vascularis due to aging appears to be slower than spiral ligament. C.

Digenic inheritance of deafness caused by mutations in genes encoding cadherin 23 and protocadherin 15 in mice and humans

Mutations in genes coding for cadherin 23 and protocadherin 15 cause deafness in both mice and humans. Here, we provide evidence that mutations at these two cadherin loci can interact to cause hearing loss in digenic heterozygotes of both species. Using a classical genetic approach, we generated mice that were heterozygous for both Cdh23 and Pcdh15 mutations on a uniform C57BL/6J background. Significant levels of hearing loss were detected in these mice when compared to age-matched single heterozygous animals or normal controls. Cytoarchitectural defects in the cochlea of digenic heterozygotes, including degeneration of the stereocilia and a base-apex loss of hair cells and spiral ganglion cells, were consistent with the observed age-related hearing loss of these mice beginning with the high frequencies. In humans, we also have obtained evidence for a digenic inheritance of a USH1 phenotype in three unrelated families with mutations in CDH23 and PCDH15. Altogether, our data indicate that CDH23 and PCDH15 play an essential long-term role in maintaining the normal organization of the stereocilia bundle.

The effects of superoxide dismutase in gerbils with bacterial meningitis

Inflammatory products, such as oxygen radicals generated during the course of bacterial meningitis, can damage nerve endings, hair cells, and/or supporting cells in the cochlea. Superoxide dismutase (SOD), an O2-scavenger, has been shown to play an important role in the protection against radical toxicity in various animal experiments. To study the antioxidant effects of SOD on the inflammatory response of gerbils with bacterial meningitis. Meningitis was induced in three groups of 10 gerbils by intrathecal (IT) injection of Streptococcus pneumoniae into the cisterna magna. Group 1 received IT SOD, group 2 received intramuscular (IM) SOD, and group 3, the control group, received IM normal saline. Histologic data and auditory brainstem responses (ABR) were obtained from each gerbil. Fibrosis and/or neo-ossification were near absent in the IT SOD group and significantly less fibrosis occurred in the IM group (IT vs. IM: P = 0.010; IT vs. control group: P = 0.001). The amount of surviving spiral ganglion cells correlated inversely with the extent of fibrosis (r = -0.753, P < 0.00001). IT injection of SOD significantly reduced cochlear fibrosis and neo-ossification, reduced the spiral ganglion cell loss, and decreased damage of the cochlear components following bacterial meningitis.

Reduction of acute cisplatin ototoxicity and nephrotoxicity in rats by oral administration of allopurinol and ebselen

Cisplatin ototoxicity has been associated with the generation of toxic levels of reactive oxygen species (ROS) which can lead to injury or loss of outer hair cells in the organ of Corti, damage to the stria vascularis, and loss of spiral ganglion cells, resulting in permanent hearing loss. In an attempt to reduce the formation of ROS and to bolster the innate oxidative stress defenses of the cochlea, we tested individual and combined formulations of allopurinol, a xanthine oxidase inhibitor, and ebselen, a glutathione peroxidase mimic. We used an acute cisplatin toxicity rat model (16 mg/kg i.p.) to analyze allopurinol and ebselen alone and in combination for their ability to reduce cisplatin associated hearing loss and nephrotoxicity. The results from our studies indicate that a combined formulation of ebselen and allopurinol affords significant protection to the cochlea and kidney from cisplatin toxicity. In the cochlea, protection is dependent on the preservation of outer hair cell number, while in the kidney, protection is associated with the preservation of proximal tubular epithelia. Further evaluation of the chemoprotective effects of ebselen and allopurinol on cisplatin side effects in the presence of tumor appears warranted.

Histopathological and morphometric study of cochleosaccular dysplasia in dalmatian dogs

Problem: This study shows systematic morphometric and histopathologic analysis of temporal bones of Dalmatian dogs with cochleosaccular dysplasia at different ages in order to better understand the pathogenesis of cochleosaccular dysplasia. Methods: Three groups were selected: (1) deaf Dalmatians (1 month to 5 years); (2) 2 litters of Dalmatians from the same deaf female and same deaf male (1 day to 2 weeks); and (3) hearing age-matched Black Labradors (deafness not described in this breed). Measurements included stria vascularis and spiral ligament area counts, average density of spiral ganglion and Scarpa′s ganglion cells, and standard cytocochleograms. Reissner’s membrane (RM) was classified as normal, collapsed, or hydropic and saccules as normal or collapsed wall, and normal or abnormal otolitic membranes. Results: At 1 week, RM began to collapse close to limbus, but saccule appeared normal. By 10 days, RM and saccular wall were totally collapsed; however, saccular hair cells were preserved. After 1 week, all animals had abnormal otolitic membranes. There was total loss of hair cells in saccular macula in the 5-year-old. Spiral ganglion cells were lost in middle turn, followed by basal. Apical turn was affected only in the 5-year-old. Cochlear hair cells were present only during the first 2 weeks. Scarpa ganglion cells count showed that the normal dogs have more cells than the deaf group. Conclusion: Cochleosaccular dysplasia in this Dalmatian dogs seems to be a progressive disorder that begins with the collapse of Reissner’s membrane at the limbus followed by loss of hair cells and later the loss of spiral ganglion cells. Significance: Cochleosaccular dysplasia is considered the most common cause of profound congenital hearing impairment. Hereditary deafness in Dalmatian dogs generally appears isolated, as in human beings, making these dogs a good model for hereditary deafness. If the disease in human beings is also progressive, new therapeutic approaches could be evaluated to prevent the development of the disease. Support: None reported.

Cochleosaccular dysplasia: a morphometric and histopathologic study in a series of temporal bones.

The objective of this study was to perform a morphometric analysis of a series of temporal bones with cochleosaccular dysplasia to clarify the extent of inner ear changes in this disease. This human temporal bone histopathologic study of a series of deaf-mute cases involves morphometric analysis, including stria vascularis and spiral ligament area measurements and spiral ganglion and hair cells counts. Thirteen temporal bones were selected from 35 with deaf mutism based on the histopathologic findings described by Scheibe. Twenty normal age-matched control subjects were used for comparisons. All temporal bones had the main histopathologic findings described by Scheibe, as well as severe affected stria vascularis. Seven temporal bones had cystic areas in the stria and three had concretions. Cross-sectional strial areas in temporal bones with cochleosaccular dysplasia were smaller than normal in all cochlear turns; however, no difference was found in spiral ligament cross-sectional areas. Reissner's membrane was hydropic in three temporal bones and the organ of Corti was absent in at least one cochlear turn in five. Concretions were present in the macula of seven temporal bones. Twelve temporal bones showed some level of spiral ganglion cell loss. No hair cells were observed in any temporal bone. A familial history of deafness was found in three cases. Pathologic findings were variable and limited to the saccule and scala media. The variation, perhaps, reflects the different etiologies involved in the origin of cochleosaccular dysplasia.

Presbycusis: a human temporal bone study of individuals with flat audiometric patterns of hearing loss using a new method to quantify stria vascularis volume.

The purpose of this study was to determine the prevalence of stria vascularis atrophy in individuals with presbycusis and flat audiometric patterns of hearing loss. Individuals with presbycusis have historically been categorized by the shape of their audiograms, and flat audiometric thresholds have been reported to be associated with atrophy of the stria vascularis. Stria vascularis volume was not measured in these studies. Retrospective case review. Archival human temporal bones from individuals with presbycusis were selected on the basis of strict audiometric criteria for flat audiometric thresholds. Six temporal bones that met these criteria were identified and compared with 10 temporal bones in individuals with normal hearing. A unique quantitative method was developed to measure the stria vascularis volume in these temporal bones. The hair cell and spiral ganglion cell populations also were quantitatively evaluated. Only one of the six individuals with presbycusis and flat audiometric thresholds had significant atrophy of the stria vascularis. This individual with stria vascularis atrophy also had reduced inner hair cell, outer hair cell, and ganglion cell populations. Three of the individuals with presbycusis had spiral ganglion cell loss, three individuals had inner hair cell loss, and all six individuals had outer hair cell loss. The results of this investigation suggest that individuals with presbycusis and flat audiometric patterns of hearing loss infrequently have stria vascularis atrophy. Outer hair cell loss alone or in combination with inner hair cell or ganglion cell loss may be the cause of flat audiometric thresholds in individuals with presbycusis.

Allografted fetal dorsal root ganglion neuronal survival in the guinea pig cochlea

Neural grafting is a potential strategy to help restore auditory function following loss of spiral ganglion cells. As a first step towards the reconstruction of a neural pathway from the cochlea to the brainstem, we have examined the survival of fetal dorsal root ganglion (DRG) neurons allografted into the cochlea of adult guinea pigs. In some animals implantation of DRGs was combined with a local infusion of neurotrophic substances whereas in others auditory sensory receptors were chemically destroyed prior to DRG implantation by injection of the ototoxin neomycin into the middle ear. The results show that many transplanted DRG neurons attached close to the cochlear spiral ganglion neurons. The survival of the implant was significantly increased by treatment with neurotrophic factors, but not reduced by the absence of auditory sensory structures. This study shows that implanted sensory neurons can survive heterotopic grafting immediately adjacent to the eighth cranial nerve, thereby providing a basis for further studies of the anatomical and functional influence of neural grafts in the inner ear.

Histopathology of cochlear implants in humans.

The insertion of an intrascalar electrode array during cochlear implantation causes immediate damage to the inner ear and may result in delayed onset of additional damage that may interfere with neuronal stimulation. To date, there have been reports on fewer than 50 temporal bone specimens from patients who had undergone implantation during life. The majority of these were single-channel implants, whereas the majority of implants inserted today are multichannel systems. This report presents the histopathologic findings in temporal bones from 8 individuals who in life had undergone multichannel cochlear implantation, with particular attention to the type and location of trauma and to long-term changes within the cochlea. The effect of these changes on spiral ganglion cell counts and the correlation between speech comprehension and spiral ganglion cell counts were calculated. In 4 of the 8 cases, the opposite, unimplanted ear was available for comparison. In 3 of the 4 cases, there was no significant difference between the spiral ganglion cell counts on the implanted and unimplanted sides. In addition, in this series of 8 cases, there was an apparent negative correlation between residual spiral ganglion cell count and hearing performance during life as measured by single-syllable word recognition. This finding suggests that abnormalities in the central auditory pathways are at least as important as spiral ganglion cell loss in limiting the performance of implant users.

Temporal Bone Histopathologic and Genetic Studies in Mohr-Tranebj??rg Syndrome (DFN-1)

To describe the temporal bone histopathologic and genetic abnormalities in a case of Mohr-Tranebjaerg syndrome. Mohr-Tranebjaezrg syndrome (DFN-1) is an X-linked, recessive, syndromic hearing loss, characterized by postlingual sensorineural hearing loss with onset in childhood, followed in adult life by progressive dystonia, spasticity, dysphagia, and optic atrophy. The syndrome is caused by mutations in the DDP (deafness/dystonia peptide) gene, which are thought to result in mitochondrial dysfunction with subsequent neurodegeneration. The temporal bone pathologic changes in this syndrome have not been reported. Hearing loss developed in the patient at age 4, blindness at age 48, and dystonia at age 57. Genetic studies on peripheral blood showed a l51delT mutation in his DDP gene. He died at age 66. The right temporal bone was subjected to light microscopy and polymerase chain reaction-based analysis of the DDP gene sequence. There was near complete loss of spiral ganglion cells with loss of nearly all peripheral and central processes. Only 1,765 spiral ganglion cells remained (8.5% of mean normal for age). The organ of Corti (including hair cells), stria vascularis, and spiral ligament were preserved. There was also a severe loss of Scarpa's ganglion cells with preservation of vestibular hair cells. The population of geniculate and trigeminal ganglion cells appeared normal. Sequence analysis from temporal bone DNA showed the 15ldelT DDP gene mutation. Sensorineural hearing loss in Mohr-Tranebjaerg syndrome is the result of a postnatal, progressive, severe auditory neuropathy.

Menière's disease as a manifestation of vestibular ganglionitis

Objective: To present morphologic evidence of viral-induced vestibular nerve pathology in Menière's Disease (MD). Material Studied: Twelve temporal bones (TB) from 8 patients with the clinical symptoms of MD. Results: There was endolymphatic hydrops (EH) and perilymphatic fibrosis in 10 of the 12 TB from MD patients. Of the 10 TB with EH of the pars inferior, 3 also contained outpouchings in the pars superior (utricle and canals), and 3 showed apical spiral ganglion cell loss. Focal vestibular nerve axonal degeneration was observed in all but one TB. Conclusion: Morphologic changes in TB of patients with MD, and clinical observations in patients with recurrent vestibulopathy, support the concept that the pathologic mechanism responsible for auditory and vestibular symptoms in MD may be reactivation of a latent viral vestibular ganglionitis. (Am J Otolaryngol 2001;22:241-250. Copyright © 2001 by W.B. Saunders Company)

Anatomical, Metabolic and Genetic Aspects of Age-related Hearing Loss in Mice: Aspectos anatómicos, metabólicos y genéticos de la hipoacusia relacionada con la edad en ratones

Because of their short lifespan and genetic homogeneity, mice can provide valuable insights into the biological basis of age-related hearing loss. In C57BL/6 mice, hair cell loss begins around 1–2 months of age and progresses rapidly along a base-to-apex gradient, whereas CBA mice show relatively little hair cell loss until late in life. This anatomical difference is reflected in dehydrogenase histochemistry, an indirect measure of aerobic energy metabolism. A small, but significant, decrease in hair cell dehydrogenase staining occurred in CBA mice between 1.5 and 18 months of age. Significantly, dehydrogenase levels in 1.5-month C57 mice were substantially lower than in CBA mice of any age. Thus, deficits in aerobic energy metabolism presage degeneration of the hair cells. The superoxide radical, O2−, a normal byproduct of cellular metabolism, is potentially toxic and can cause cellular damage if it is not inactivated by superoxide dismutases. Cytosolic copper/zinc superoxide dismutase (SOD 1) is highly expressed in the cochlea. Knockout mutant mice with a single (HET) or double deletion (KO) of the Sodl gene coding for SOD1 showed greater age-related losses than wild-type (WT) mice. KO mice had the worst hearing, WT the best, and HETs were intermediate. KOs exhibited considerably greater hair cell loss than WT mice; however, losses in KOs were only slightly greater than in HETs. KO mice showed significantly greater loss of spiral ganglion cells and nerve fibers than WT mice. These results indicate that SOD1 and O2− play important roles in age-related hearing loss. Intervention strategies targeting O2− may reduce age-related hearing loss.

Effectiveness of preoperative administration of an N-methyl-D-aspartate antagonist to enhance cochlear neuron resistance to intraoperative traumatic stress: an experimental study.

Cochlear neurons are inevitably exposed to traumatic stress during surgical removal of an acoustic neuroma; that event is an important cause of postoperative cochlear neuronal degeneration, with subsequent loss of spiral ganglion cells (SGCs). The object of this study was to investigate whether preoperative pharmacological treatment can enhance the resistance of cochlear neurons to the traumatic stress of surgery. Cochlear neuronal degeneration was induced in 17 rats by controlled compression of the cerebellopontine angle portion of the cochlear nerve. Dizocilpine maleate (MK-801; 10 mg/kg), an N-methyl-D-aspartate (NMDA) antagonist, was administered intraperitoneally to six of the 17 rats 30 minutes before compression occurred. Two weeks after compression, each rat was killed, and the numbers of SGCs in histological preparations of temporal bones were counted. Spiral ganglion cells were more numerous in rats administered dizocilpine maleate (p < 0.03) than in rats that did not receive treatment, indicating that receptor-mediated glutamate neurotoxicity may participate in the pathogenesis of trauma-induced cochlear neuron death and that administration of an NMDA antagonist before surgery may protect the nerve from injury leading to hearing loss.