Macrophage depletion attenuates degeneration of spiral ganglion neurons in kanamycin-induced unilateral hearing loss model.

Pathological conditions in cochlea, such as ototoxicity, acoustic trauma, and age-related cochlear degeneration, induce cell death in the organ of Corti and degeneration of the spiral ganglion neurons (SGNs). Although macrophages play an essential role after cochlear injury, its role in the SGNs is limitedly understood. We analyzed the status of macrophage activation and neuronal damage in the spiral ganglion after kanamycin-induced unilateral hearing loss in mice. The number of ionized calcium-binding adapter molecule 1 (Iba1)-positive macrophages increased 3 days after unilateral kanamycin injection. Macrophages showed larger cell bodies, suggesting activation status. Interestingly, the number of activating transcription factor 3 (ATF3)-positive-neurons, an indicator of early neuronal damage, also increased at the same timing. In the later stages, the number of macrophages decreased, and the cell bodies became smaller, although the number of neuronal deaths increased. To understand their role in neuronal damage, macrophages were depleted via intraperitoneal injection of clodronate liposome 24 h after kanamycin injection. Macrophage depletion decreased the number of ATF3-positive neurons at day 3 and neuronal death at day 28 in the spiral ganglion following kanamycin injection. Our results suggest that suppression of inflammation by clodronate at early timing can protect spiral ganglion damage following cochlear insult.

Alterations in gray matter volume due to unilateral hearing loss.

Although extensive research on neural plasticity resulting from hearing deprivation has been conducted, the direct influence of compromised audition on the auditory cortex and the potential impact of long durations of incomplete sensory stimulation on the adult cortex are still not fully understood. In this study, using voxel-based morphometry, we evaluated gray matter (GM) volume changes that may be associated with reduced hearing ability and the duration of hearing impairment in 42 unilateral hearing loss (UHL) patients with acoustic neuromas compared to 24 normal controls. We found significant GM volume increases in the somatosensory and motor systems and GM volume decreases in the auditory (i.e., Heschl's gyrus) and visual systems (i.e., the calcarine cortex) in UHL patients. The GM volume decreases in the primary auditory cortex (i.e., superior temporal gyrus and Heschl's gyrus) correlated with reduced hearing ability. Meanwhile, the GM volume decreases in structures involving high-level cognitive control functions (i.e., dorsolateral prefrontal cortex and anterior cingulate cortex) correlated positively with hearing loss duration. Our findings demonstrated that the severity and duration of UHL may contribute to the dissociated morphology of auditory and high-level neural structures, providing insight into the brain's plasticity related to chronic, persistent partial sensory loss.

Vulnerability to acoustic trauma in the normal hearing ear with contralateral hearing loss.

OBJECTIVES: We undertook an animal study to investigate the functional and histological changes that occur in the normal hearing ear of following acoustic trauma. METHODS: As an animal model of unilateral hearing loss, the right ears of CBA mice were deafened by cochlear destruction at 6 weeks of age (SSD group). The control groups included mice that underwent a sham surgery, and mice that were exposed to noise binaurally and monaurally (by plugging the right ear completely). At 10 weeks of age, all mice were exposed to acoustic trauma (110 dB sound pressure level for 1 hour) that induced a transient threshold shift (TTS). Changes in the hearing thresholds of the left ear were assessed over the next 4 weeks by measuring the auditory brainstem responses (ABRs) and distortion product otoacoustic emissions (DPOAEs). RESULTS: Following the noise exposure, the SSD group showed a permanent threshold shift (PTS) of about 10 dB, whereas the other groups showed full recovery from the TTS. The threshold of the DPOAEs of the left ears were increased after noise exposure but returned to normal in all groups, with no significant differences among the groups. Histological evaluation showed no apparent cellular loss or apoptosis in the left ears of all groups, including the SSD group. CONCLUSIONS: These results suggest that normal hearing ears are more vulnerable to acoustic trauma following contralateral unilateral cochlear ablation. This increased vulnerability may be due to damaged neural structures.

Ectopic pituitary adenoma associated with an empty sella presenting with hearing loss: case report with literature review.

Ectopic pituitary adenomas are uncommon entities that may pose substantial diagnostic challenges. In the majority of these cases, patients present with endocrine and/or nasal obstruction symptoms. We report the case of an ectopic pituitary adenoma in a 76-year-old man with an empty sella who initially presented with right-sided hearing loss progressing to bilateral hearing loss over the next 4 years. Neuroimaging studies revealed a large, expansile central skull base mass replacing the clivus and sphenoid sinus, and invading the internal auditory canals and inner ear bilaterally. The tumor also involved the floor of the middle cranial fossae and bilateral medial temporal and occipital bones. Histopathologic examination, including immunohistochemical studies, revealed a sparsely granulated lactotroph adenoma. Hearing loss in a patient with ectopic pituitary adenoma constitutes an extremely unusual presentation. This case was further complicated by the presence of an empty sella and the absence of symptoms related to hyperprolactinemia.

Screening of SLC26A4, FOXI1 and KCNJ10 genes in unilateral hearing impairment with ipsilateral enlarged vestibular aqueduct.

OBJECTIVE: To investigate the implication of SLC26A4, FOXI and KCNJ10 genes in unilateral hearing impairment associated with ipsilateral inner ear malformation (Enlargement of the vestibular aqueduct and/or Mondini dysplasia). METHODS: We have gathered 25 patients presenting unilateral hearing impairment and ipsilateral enlarged vestibular aqueduct. For each of the patients, we have analyzed SLC26A4, FOXI1 and KCNJ10 genes sequences. RESULTS: The analysis of SLC26A4 revealed only eight heterozygous SLC26A4 sequence variants, three of them being novel (p.Met147Ile, p.Asn538Asn and p.Leu627Arg). None of the patients carried a second mutation on the other allele. Moreover, the SLC26A4 locus was excluded by segregation analysis in two families. No mutations were present in FOXI1 and KCNJ10 genes. CONCLUSIONS: Together, these data suggest that SLC26A4, FOXI1 and KCNJ10 are not major determinants in unilateral deafness and enlarged vestibular aqueduct compared with their implication in Pendred syndrome and non-syndromic bilateral enlarged vestibular aqueduct.

Response of the flat cochlear epithelium to forced expression of Atoh1.

Following hair cell elimination in severely traumatized cochleae, differentiated supporting cells are often replaced by a simple epithelium with cuboidal or flat appearance. Atoh1 (previously Math1) is a basic helix-loop-helix transcription factor critical to hair cell differentiation during mammalian embryogenesis. Forced expression of Atoh1 in the differentiated supporting cell population can induce transdifferentiation leading to hair cell regeneration. Here, we examined the outcome of adenovirus mediated over-expression of Atoh1 in the non-sensory cells of the flat epithelium. We determined that seven days after unilateral elimination of hair cells with neomycin, differentiated supporting cells are absent, replaced by a flat epithelium. Nerve processes were also missing from the auditory epithelium, with the exception of infrequent looping nerve processes above the habenula perforata. We then inoculated an adenovirus vector with Atoh1 insert into the scala media of the deafened cochlea. The inoculation resulted in upregulation of Atoh1 in the flat epithelium. However, two months after the inoculation, Atoh1-treated ears did not exhibit clear signs of hair cell regeneration. Combined with previous data on induction of supporting cell to hair cell transdifferentiation by forced expression of Atoh1, these results suggest that the presence of differentiated supporting cells in the organ of Corti is necessary for transdifferentiation to occur.

Tuberculous meningitis-induced unilateral sensorineural hearing loss: a temporal bone study.

The relationship between meningitis and sensorineural hearing loss (SNHL) has long been studied. Many histopathological studies of animal models and human temporal bones with respect to bacterial meningitis have been carried out. However, the relationship between SNHL and tuberculous meningitis was seldom addressed and the pathophysiology remains unclear. We carried out temporal bone studies on material from a 22-year-old patient who developed a right unilateral SNHL before dying from tuberculous meningitis. The histopathological findings for the right temporal bone were as follows: (1) inflammation mainly appeared in the internal auditory canal, modiolus and Rosenthal's canal and extended to the osseous spiral ligament, whereas the perilymphatic spaces were less involved; (2) the organ of Corti, cochlear nerve fibres and spiral ganglion cells were severely degenerated, particularly in the basal and middle turns; (3) the contralateral side (for which the patient had no complaints) showed an inner space free from inflammation, but some granulomatous formations were observed in the middle ear cavity. We conclude that the modiolus and cochlear aqueduct are the main routes for the spread of infection from the meninges to the inner ear. The progression of hearing loss resembles that of bacterial meningitis and shares attributes of retrocochlear SNHL.