Extent Of Hair Cell Damage Research Articles

A comprehensive characterizations of zebrafish rheotactic behaviors and its application to otoprotective drug screening

Aquatic animals have rheotaxis that maintains a balance in response to water flow.They sense water flow through hair cells in lateral line, thereby leading to behavior changes relevant to damages on hair cells, the primary sensory receptor cells within auditory and vestibular systems.Zebrafish are efficient animal models for high-throughput drug screening with human-like hair cells along the lateral line. Their rheotactic behaviors could be assays for hair-cell-targeted drug screening. However,knowledge and tools for rheotaxis analysis along the extent of hair-celldamage have not beenfullyinvestigated. Thisarticleaims atcharacterization of rheotactic behaviorsidentifyinglateral linestatesviaananalysis platformthatsimultaneously examinesmultiple zebrafish larvae.To this end, we developed anautomated framework that incorporated animal test hardware equipment and real-time analysis software for monitoring aquatic behaviors of multiple larvae. Through this framework, a commensurable measure for one-dimensional characterization of rheotactic behaviors was consolidated so that its linear changes could be associated with the population of hair cells remaining intact. Thesefindingssatisfied requestsfor an automated analysis platform to conduct large-scale screening anda biomarkerthatdiscriminatethe seriousness of haircell damagetoscreen candidates having significant effectsinotoprotectivedrug discovery.

Novel Peptide Vaccine GV1001 Rescues Hearing in Kanamycin/Furosemide-Treated Mice.

The cell-penetrating peptide GV1001 has been investigated as an anticancer agent and recently demonstrated anti-oxidant and anti-inflammatory effects. It has shown a protective effect on a kanamycin (KM)-induced ototoxicity mouse model. In the present study, we administered GV1001 at different time points after inducing hair cell damage, and examined if it rescues hair cell loss and restores hearing. A deaf mouse model was created by intraperitoneal injection of KM and furosemide. First, to test the early temporal change of hearing and extent of hair cell damage after KM and furosemide injection, hearing and outer hair cells (OHCs) morphology were evaluated on day 1, day 2 and day 3 after injection. In the second experiment, following KM and furosemide injection, GV1001, dexamethasone, or saline were given for three consecutive days at different time points: D0 group (days 0, 1, and 2), D1 group (days 1, 2, and 3), D3 group (days 3, 4, and 5) and D7 group (days 7, 8, and 9). The hearing thresholds were measured at 8, 16, and 32 kHz before ototoxic insult, and 7 days and 14 days after KM and furosemide injection. After 14 days, each turn of the cochlea was imaged to evaluate OHCs damage. GV1001-treated mice showed significantly less hearing loss and OHCs damage than the saline control group in the D0, D1 and D3 groups (p < 0.0167). However, there was no hearing restoration or intact hair cell in the D7 group. GV1001 protected against cochlear hair cell damage, and furthermore, delayed administration of GV1001 up to 3 days rescued hair cell damage and hearing loss in KM/furosemide-induced deaf mouse model.

Cochlear damage caused by continuous and intermittent noise exposure

We compared the extent of permanent threshold shifts (PTS) and cochlear hair cell damage caused by continuous noise exposure with those caused by intermittent noise exposure. Twenty male pigmented guinea pigs that had been exposed to a one-octave band of noise at 4 kHz for 5 h were placed in four groups: exposure to 115 dB SPL continuous noise (group 1, n=5), 115 dB SPL intermittent noise (group 2, n=5), 125 dB SPL continuous noise (group 3, n=5), and 125 dB SPL intermittent noise (group 4, n=5). PTS at 2, 4, 8, and 16 kHz were assessed by means of auditory brainstem responses measured before noise exposure and 10 days after. The guinea pigs were killed 15 days after noise exposure, and the number of hair cells missing counted in surface preparations of the organs of Corti stained with rhodamine phalloidin. Groups 1 and 3 had significantly greater PTS ( P<0.05) at all frequencies than intermittent groups 2 and 4. Group 3 had the greatest PTS at all the frequencies. Intermittent 125 dB noise total energy was greater than that of continuous 115 dB noise, but the latter elicited more PTS than the former. The extent of hair cell damage was comparable to the physiological findings. This indicates that continuous noise causes greater damage to the cochlea than intermittent noise of the same intensity and that, at the intensities tested, damage to the cochlea is not proportional to the total noise energy.

Acquired resistance to acoustic trauma by sound conditioning is primarily mediated by changes restricted to the cochlea, not by systemic responses

Hearing loss caused by intense sound exposure can be significantly reduced by pre-exposing subjects to moderate-level acoustic stimuli. This phenomenon occurs in a variety of mammals. We investigated whether sound conditioning provides acquired resistance to acoustic trauma through local mechanisms selectively in the conditioned ears or if systemic mechanisms are involved that would yield contralateral protection in unconditioned ears. Guinea pigs (group I) in which one external ear canal was occluded were exposed to conditioning sound (2–20 kHz, 85 dB SPL, 5 h/day, 10 days). After removing the occlusion, the animals were then subjected bilaterally to intense noise (2–20 kHz, 110 dB SPL, 5 h) 5 days after the last conditioning exposure. Animals without ear canal occlusion were also exposed to the intense sound without conditioning (group II) or following the same conditioning exposure (group III). Intense sound exposure caused significantly greater permanent ABR threshold shifts at all frequencies tested (4, 8, 12, 16 and 20 kHz) in group II than in group III. In group I, the occluded ears showed significantly greater threshold shifts at all frequencies compared to the unoccluded ears. The threshold shifts in the occluded ears in group I were identical to those observed in group II; and the shifts in unoccluded ears in group I were identical to those in group III. Protective effects provided by sound conditioning were almost the same in group III and in the unoccluded ears in group I. The extent of hair cell damage supported the physiological findings. These results indicate that acquired resistance to acoustic trauma provided by sound conditioning is restricted to the cochlea exposed to conditioning sound, suggesting that conditioning protection is mediated primarily by the changes that occur locally within the conditioned cochlea. This animal model, with unilateral external ear canal occlusion during sound conditioning, is useful for studies of the mechanisms of conditioning protection.

Anatomical effects of intense tone stimulation in the goldfish ear: Dependence on sound‐pressure level and frequency

The final results of an experimental investigation to study the extent of frequency regionalization in the ear of goldfish are presented. Goldfish about 6 in. in body length were subjected to intense tones at 250 and 500 Hz, and four different sound‐pressure levels. They were placed in a waveguide and constrained as close as possible to a pressure antinode so that the primary response of the inner ear was due to the induced motion of the swimbladder and Weberian ossicles. Both saccular and lagenar maculae were examined under a scanning electron microscope to determine the location and extent of hair cell damage as a function of frequency and sound‐pressure level. The results are not inconsistent with the gross frequency regionalization in the saccular macula of codfish determined by P. S. Enger [Hearing and Sound Communication in Fishes (Springer, New York, 1981), pp. 243–255]. In addition, the results indicate a possible breakdown of the Weberian apparatus at extremely high sound‐pressure levels where the primary site of damage switches from the saccule to lagena. This is consistent with the behavior of the system based on its viscoelastic properties as postulated by R. McN. Alexander [J. Exp. Biol. 38, 747–757 (1961)]. Work supported in part by ONR and NIH.]

Hair cell damage produced by acoustic trauma in the chick cochlea

Examination of pure-tone acoustic damage in the chick hasilar papilla revealed that the location and extent of hair cell damage was a function of both the stimulus intensity and the age at which the chicks were exposed. Scanning electron microscopic evaluation of noise-exposed cochleae at post-hatching days 1, 10 and 30 permitted the identification of discrete regions of damage, including hair cells with stereocilia injuries as well as those lost from the epithelium. The hair cell damage was tonotopically distributed along the cochlea according to frequency. However, for each exposure frequency two distinct sites of damage were often produced, and their locations were correlated with stimulus intensity. At low intensities, a longitudinal strip of hair cell damage ran along the superior edge of the basilar papilla. As exposure intensity increased, a second damage site developed along the inferior edge of the basilar papilla, distal to the longitudinal strip. This second type of damage initially took the form of a series of laterally-oriented wedges, but at higher intensities, the wedges coalesced to form a large crescent-shaped patch of damage. The location of the damage sites for each frequency did not shift with age. However, there were differences in the extent and position of the damage which could be correlated with stimulus intensity and with changes in middle ear admittance during development [(1983) Development of Auditory and Vestibular Systems, pp. 3–25. Editor: R Romand. Academic Press, New York]. These results suggest that developmental changes in the location and extent of hair cell damage depend on the effective stimulus intensity reaching the cochlea, rather than on alterations in the frequency coding of the hair cells.

Comparative ototoxicity of gentamicin and sisomicin in the cat

Comparative ototoxicity of gentamicin and sisomicin in the cat

Ototoxicity of Lividomycin

Ototoxicity of lividomycin (LVM), recently developed aminoglycoside antibiotic, was functionally as well as histopathologically evaluated in guinea pigs of Hartley strain (300g body weight at the start of the experiment). Sixty three guinea pigs were divided into following 5 groups.Group 1 (10 guinea pigs), each animal received LVM intramuscularly at dosis of 100mg/kg body weight.Group 2 (21 guinea pigs), each received LVM intramuscularly at dosis of 200mg/kg.Group 3 (11 guinea pigs), each received LVM intramuscularly at dosis of 400mg/kg.Group 4 (10 guinea pigs), each received KM intramuscularly at dosis of 100mg/kg.Group 5 (11 guinea pigs), each received KM intramuscularly at dosis of 200mg/kg.The antibiotics were given to the animals for 4 weeks. Pinna reflex test was performed before, during and after the experiment with audiometer. Frequencies of the audiometer ranged from 10, 000Hz to 500Hz. The animals underwent vital fixation with Wittmaack's fixative under general anesthesia after the end of the experiment. The temporal bones were en bloc removed from the skull and further fixed in the same fixative for one week. The temporal bones were embeded in celloidin after decalcification. The horizontally sectioned serial celloidin sections were stained with hematoxylin-eosin. Histopathological examination was performed on the spiral organ of the cochlea and the vestibular organ, with special reference to the extent of hair cell damage in the cochlea. The results obtained were as follows:1) LVM was ototoxic in guinea pigs at the dosis of 200 and 400mg per kg body weight. The ototoxicity was much prominent in the hair cells of the spiral organ. In the basal turn of the cochlea the outer hair cells were more sensitive to the antibiotic than the inner hair cells, but in the apical and 4th turns the inner hair cells were more vulnerable than the outer ones. The loss of the outer hair cells, that is advanced damage, started from the basal end and indicated a general tendency to spread upwards.2) LVM showed almost the same ototoxicity as KM at the dosis of 200mg/kg body weight in guinea pigs.