3D MRI of the membranous labyrinth. An age related comparison of MR findings in patients with labyrinthine fibrosis and in persons without inner ear symptoms. (1/37)

PURPOSE: We compared MRI of the membranous labyrinth in patients with chronic non-neoplastic inner ear disease and MR signs of labyrinthine fibrosis and controls depending on their age, in order to establish whether there were any MR differences regarding patient age groups, control age groups and between the patients and controls themselves. MATERIALS AND METHODS: Clinical ENT examinations as well as a T2* weighted 3D CISS (Constructive Interference in Steady State) sequence with a slice thickness of 0.7 mm were performed. Our collective was subdivided as follows: 0-19 years (10 controls, 3 patients with chronic non-neoplastic inner ear disease), 20-49 years (55 controls, 8 patients), 50 years and older (40 controls, 22 patients). Detectability of labyrinthine structures (e.g. cochlea, vestibule, semicircular canals) and filling defects were evaluated. RESULTS: In the 3 age-groups of the control collective no significant differences were observed in the membranous labyrinth. However differences concerning labyrinthine detectability emerged between controls and patients in both the 20-49 years and 50 years and older age groups. In the patient collective the 3 age groups showed no significant discrepancy in the mean number of lesions. CONCLUSION: Filling defects of the membranous labyrinth on 3D CISS MR images are pathological even in older persons. We would therefore recommend high resolution T2* weighted MRI in the case of suspected labyrinthine fibrosis.  (+info)

Ototoxicity: an argument for evaluation of the cochlea in safety testing in animals. (2/37)

The cochlea is one of the more common targets for toxic effects, yet current toxicologic screening in animals does not routinely evaluate the cochlea as a potential target organ. Although histopathologic sections are routinely taken from the eye and the optic nerve and tract and most studies include at least 1 section through the nasal cavity and olfactory mucosa, the cochlea is not histopathologically examined in routine toxicity studies. Unfortunately, routine clinical examinations frequently miss ototoxicity because rodents and other species can lose most of their high-frequency hearing and still respond to most ambient noises. Ototoxicity as a deficiency in toxicologic screening can be remedied by using well-established histopathologic and behavioral methods or electrophysiologic methods, such as brain stem auditory evoked responses (BAERs). Once the equipment is in place, BAERs can be obtained quickly and easily for ototoxicity screening (approximately 15 minutes for paired testing of 2 rats and 30 minutes each for dogs). BAERs also can be used in virtually all mammalian species. Three or 4 probe frequencies (eg, 4, 8, 16, and 32 kHz), representing different areas of the cochlea, can be tested in a few minutes with subcutaneous electrodes under short-acting chemorestraint. Given the availability of several approaches to screening for ototoxicity and the importance of the auditory function in human health, safety tests of chemicals and drugs should include an effective screening test for ototoxicity.  (+info)

Spiral ligament pathology: a major aspect of age-related cochlear degeneration in C57BL/6 mice. (3/37)

Data from systematic, light microscopic examination of cochlear histopathology in an age-graded series of C57BL/6 mice (1.5-15 months) were compared with threshold elevations (measured by auditory brain stem response) to elucidate the functionally important structural changes underlying age-related hearing loss in this inbred strain. In addition to quantifying the degree and extent of hair cell and neuronal loss, all structures of the cochlear duct were qualitatively evaluated and any degenerative changes were quantified. Hair cell and neuronal loss patterns suggested two degenerative processes. In the basal half of the cochlea, inner and outer hair cell loss proceeded from base to apex with increasing age, and loss of cochlear neurons was consistent with degeneration occurring secondary to inner hair cell loss. In the apical half of the cochlea with advancing age, there was selective loss of outer hair cells which increased from the middle to the extreme apex. A similar gradient of ganglion cell loss was noted, characterized by widespread somatic aggregation and demyelination. In addition to these changes in hair cells and their innervation, there was widespread degeneration of fibrocytes in the spiral ligament, especially among the type IV cell class. The cell loss in the ligament preceded the loss of hair cells and/or neurons in both space and time suggesting that fibrocyte pathology may be a primary cause of the hearing loss and ultimate sensory cell degeneration in this mouse strain.  (+info)

Delayed inner ear maturation and neuronal loss in postnatal Igf-1-deficient mice. (4/37)

Insulin-like growth factor-1 (IGF-1) has been shown to play a key role during embryonic and postnatal development of the CNS, but its effect on a sensory organ has not been studied in vivo. Therefore, we examined cochlear growth, differentiation, and maturation in Igf-1 gene knock-out mice at postnatal days 5 (P5), P8, and P20 by using stereological methods and immunohistochemistry. Mutant mice showed reduction in size of the cochlea and cochlear ganglion. An immature tectorial membrane and a significant decrease in the number and size of auditory neurons were also evident at P20. IGF-1-deficient cochlear neurons showed increased caspase-3-mediated apoptosis, along with aberrant expression of the early neural markers nestin and Islet 1/2. Cochlear ganglion and fibers innervating the sensory cells of the organ of Corti presented decreased levels of neurofilament and myelin P(0) in P20 mouse mutants. In addition, an abnormal synaptophysin expression in the somata of cochlear ganglion neurons and sensory hair cells suggested the persistence of an immature pattern of synapses distribution in the organ of Corti of these animals. These results demonstrate that lack of IGF-1 in mice severely affects postnatal survival, differentiation, and maturation of the cochlear ganglion cells and causes abnormal innervation of the sensory cells in the organ of Corti.  (+info)

Dynamics of noise-induced cellular injury and repair in the mouse cochlea. (5/37)

To assess the dynamics of noise-induced tissue injury and repair, groups of CBA/CaJ mice were exposed to an octave-band noise for 2 hours at levels of 94, 100, 106, 112, or 116 dB SPL and evaluated at survival times of 0, 12, 24 hours or 1, 2, or 8 weeks. Functional change, assessed via auditory brainstem response (ABR), ranged from a reversible threshold shift (at 94 dB) to a profound permanent loss (at 116 dB). Light microscopic histopathology was assessed in serial thick plastic sections and involved quantitative evaluation of most major cell types within the cochlear duct, including hair cells (and their stereocilia), supporting cells, ganglion cells, spiral ligament fibrocytes, spiral limbus fibrocytes, and the stria vascularis. Morphometry allowed patterns of damage to be systematically assessed as functions of (1) cochlear location, (2) exposure level, and (3) postexposure survival. Insights into mechanisms of acute and chronic noise-induced cellular damage are discussed.  (+info)

Acrylonitrile produces transient cochlear function loss and potentiates permanent noise-induced hearing loss. (6/37)

There is growing evidence that agents that produce oxidative stress in the cochlea have significant ototoxic potential by themselves and can potentiate noise-induced hearing loss as well. Acrylonitrile (ACN) metabolism entails conjugation with glutathione, resulting in rapid and pronounced depletion of this important antioxidant in many organs including brain, liver, and kidney. ACN metabolism also results in cyanide (CN) formation through a secondary oxidative pathway. The results of two physiological experiments are reported here. First, the acute effects of ACN (50 mg/kg sc) on auditory sensitivity are assessed using a within subject study. In the second study, persistent effects of ACN alone (50 mg/kg, sc and 2 x 50 mg/kg, sc) and ACN in combination with noise exposure (8 h, 108 dB octave-band noise) are evaluated using threshold sensitivity as the dependent measure. Auditory threshold shift and absolute thresholds were determined using the compound action potential (CAP) amplitude. Acute ACN administration produces a loss in auditory threshold sensitivity that reached a maximum 10-20 min following sc injection. Auditory thresholds returned to control levels 75-100 min following exposure. In the study of permanent auditory threshold shifts, ACN plus noise increased auditory threshold impairment relative to rats receiving noise only when thresholds were assessed 3 weeks following exposure. ACN by itself did not produce permanent threshold impairment 3 weeks following administration. Assays were undertaken in separate groups of rats to track the elevation in blood CN and the depletion of total glutathione in cochlea, brain, and liver following ACN treatment. Systemic blood CN levels were not significantly elevated until 60-120 min following injection, and cochlear glutathione levels showed significant depletion as little as 15 min after injection and remained depressed for about 4 h. The results confirm the prediction that ACN is acutely ototoxic and can enhance noise-induced hearing loss.  (+info)

Myo15 function is distinct from Myo6, Myo7a and pirouette genes in development of cochlear stereocilia. (7/37)

The unconventional myosin genes Myo15, Myo6 and Myo7a are essential for hearing in both humans and mice. Despite the expression of each gene in multiple organs, mutations result in identifiable phenotypes only in auditory or ocular sensory organs. The pirouette (pi) mouse also exhibits deafness and an inner ear pathology resembling that of Myo15 mutant mice and thus may be functionally related to Myo15. In order to investigate possible interactions between Myo15 and Myo6, Myo7a, and the gene affected in pirouette, we crossed Myo15(sh2/sh2) mice to the three other mutant mouse strains. Hearing in doubly heterozygous mice was similar to age-matched singly heterozygous animals, indicating that partial deficiency for both Myo15 and one of these other deafness genes does not reduce hearing. Viable double mutants were obtained from each cross, indicating that potential overlapping functions between these genes in other organs are not essential for viability. All critical cell types of the cochlear sensory epithelium were present in double mutant mice and cochlear stereocilia exhibited a superimposition of single mutant phenotypes. These data suggest that the function of Myo15 is distinct from that of Myo6, Myo7a or pi in development and/or maintenance of stereocilia.  (+info)

Abnormal auditory brainstem responses and cochlear pathology in rats induced by an exaggerated styrene exposure regimen. (8/37)

Groups of 12 male 42-day-old rats were exposed to 0 or 800 ppm styrene vapors for 14 hr/day, 5 days/week for 3 weeks. Tone-pip auditory brainstem responses (ABRs) at 4, 8, 16, and 30 kHz were obtained after the last exposure. ABRs were minimally affected at 4 kHz and moderately to severely affected at 8, 16, and 30 kHz as indicated by waveforms which had a decreased amplitude and increased latency as compared to the controls. Missing outer hair cell(s) were evident in the basal and lower middle turns of the organ of Corti. Outer hair cell loss was least in the first row and greatest in the second and third rows. Occasional inner hair cells were also missing in regions of severe outer hair cell loss. The distribution of hair cell loss within the cochlea was consistent with the pattern of ABR alterations. These data document mid-frequency auditory dysfunction in styrene-exposed young adult rats with significant damage to the organ of Corti following an exaggerated styrene exposure regimen.  (+info)

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