Increased Ototoxicity in Both Young and Old Mice

Henry, Kenneth R.; Chole, Richard A.; McGinn, Michael D.; Frush, Donald P.

doi:10.1001/archotol.1981.00790380022006

Cited by 65 publications

(26 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The targets of this early magnified injury show only partial overlap: Ototoxins primarily impact hair cells and stria (Bernard 1981;Lataye et al 2004;Pryor et al 1984;Rybak et al 1991;Henley and Rybak 1995), while noise preferentially targets hair cells and neurons (Henley and Rybak 1995;Falk et al 1974;Ohlemiller et al 2000;Kujawa and Liberman 2006). The window of vulnerability also need not be the same for noise versus aminoglycosides (Henry et al 1981;Henry 1983) or even for all ototoxicants (e.g., Lataye et al 2004). The existence of somewhat different targets and timeframes for noise and ototoxic injury suggests that these operate at least partially independently.…”

Section: Kanamycin In the Early Vulnerability Windowmentioning

confidence: 99%

“…Noise vulnerability in mice appears greatest during the first month then gradually decreases up to about 4 months of age (Henry 1983). Young mice also show greater susceptibility to ototoxins (Henry et al 1981;Chen and Aberdeen 1980;Chen and Saunders 1983). Similar to the pattern for noise, vulnerability to aminoglycosides in mice appears maximal during the first month.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Protection against Noise-Induced Hearing Loss in Young CBA/J Mice by Low-Dose Kanamycin

Fernandez

Ohlemiller

Gagnon

et al. 2010

JARO

View full text Add to dashboard Cite

Animal studies indicate that a combination of kanamycin (KM) and noise produces a synergistic effect, whereby the threshold shift from the combination is greater than the sum of the shifts caused by either agent alone. Most such studies have focused on adult animals, and it has remained unclear whether younger, presumably more susceptible, animals show an even greater synergistic effect. The present study tested the hypothesis that young CBA/J mice receiving a low dose of KM (300 mg/kg, 2×/day, s.c.) from 20 to 30 days post-gestational age followed by brief noise exposure (110 dB SPL; 4-45 kHz, 30 s) would show greater noise-induced permanent threshold shifts (NIPTS) than mice receiving either treatment alone. Noise exposure produced 30-40 dB of NIPTS and moderate hair cell loss in young saline-treated mice. KM alone at this dose had no effect on thresholds. Surprisingly, mice receiving KM plus noise were protected from NIPTS, showing ABR thresholds not significantly different from unexposed controls. Mice receiving KM prior to noise exposure also showed significantly less outer hair cell loss than saline-treated mice. Additional experiments indicated protection by KM when the noise was applied either 24 or 48 h after the last KM injection. Our results demonstrate a powerful protective effect of subchronic low-dose kanamycin against NIPTS in young CBA/J mice. Repeated kanamycin exposure may establish a preconditioned protective state, the molecular bases of which remain to be determined.

show abstract

Section: Kanamycin In the Early Vulnerability Windowmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Protection against Noise-Induced Hearing Loss in Young CBA/J Mice by Low-Dose Kanamycin

Fernandez

Ohlemiller

Gagnon

et al. 2010

JARO

View full text Add to dashboard Cite

show abstract

“…Adult mice have shown little drug-induced toxicity under conditions that would produce severe auditory damage in the guinea pig or chinchilla (Forge and Schacht 2000). Existing damage protocols require repeated systemic injections of aminoglycoside to achieve HC damage (Henry et al 1981;Chen and Saunders 1983;Wu et al 2001;Jiang et al 2005Jiang et al , 2006aChu et al 2006;Staecker et al 2007). Because these protocols result in a desynchronized loss of HCs, they do not allow studies of critical early regenerative events.…”

Section: Introductionmentioning

confidence: 99%

Sox2 and Jagged1 Expression in Normal and Drug-Damaged Adult Mouse Inner Ear

Oesterle

Campbell

Taylor³

et al. 2007

JARO

218

245

View full text Add to dashboard Cite

Inner ear hair cells detect environmental signals associated with hearing, balance, and body orientation. In humans and other mammals, significant hair cell loss leads to irreversible hearing and balance deficits, whereas hair cell loss in nonmammalian vertebrates is repaired by the spontaneous generation of replacement hair cells. Research in mammalian hair cell regeneration is hampered by the lack of in vivo damage models for the adult mouse inner ear and the paucity of cell-type-specific markers for nonsensory cells within the sensory receptor epithelia. The present study delineates a protocol to drug damage the adult mouse auditory epithelium (organ of Corti) in situ and uses this protocol to investigate Sox2 and Jagged1 expression in damaged inner ear sensory epithelia. In other tissues, the transcription factor Sox2 and a ligand member of the Notch signaling pathway, Jagged1, are involved in regenerative processes. Both are involved in early inner ear development and are expressed in developing support cells, but little is known about their expressions in the adult. We describe a nonsurgical technique for inducing hair cell damage in adult mouse organ of Corti by a single high-dose injection of the aminoglycoside kanamycin followed by a single injection of the loop diuretic furosemide. This drug combination causes the rapid death of outer hair cells throughout the cochlea. Using immunocytochemical techniques, Sox2 is shown to be expressed specifically in support cells in normal adult mouse inner ear and is not affected by drug damage. Sox2 is absent from auditory hair cells, but is expressed in a subset of vestibular hair cells. Double-labeling experiments with Sox2 and calbindin suggest Sox2-positive hair cells are Type II. Jagged1 is also expressed in support cells in the adult ear and is not affected by drug damage. Sox2 and Jagged1 may be involved in the maintenance of support cells in adult mouse inner ear.

show abstract

“…Thus, it is not completely unexpected that exposure to brevetoxin-3, a potent neurotoxin, would reduce ABR amplitudes representing central auditory function rather than affect the processes of the peripheral auditory nervous system. It has long been known that mice are vulnerable to an aminoglycoside-induced hearing loss only during their pre-adult stage of development (Henry et al 1981). Recently, Schacht and his coworkers (Wu et al 2001(Wu et al , 2002 attempted to determine the appropriate dosing variables for gentamicin ototoxicity in mature mice, using a series of different drug concentrations.…”

Section: Discussionmentioning

confidence: 99%

Cochlear function in mice following inhalation of brevetoxin-3

et al. 2005

View full text Add to dashboard Cite

Brevetoxin-3 was shown previously to adversely affect central auditory function in goldfish. The present study evaluated the effects of exposure to this agent on cochlear function in mice using the 2f 1 -f 2 distortion-product otoacoustic emission (DPOAE). Towards this end, inbred CBA/CaJ mice were exposed to a relatively high concentration of brevetoxin-3 (∼400 μg/m 3 ) by nose-only inhalation for a 2-h period. Further, a subset of these mice received a second exposure a day later that lasted for an additional 4 h. Mice exposed only once for 2 h did not exhibit any notable cochlear effects. Similarly, mice exposed two times, for a cumulative dose of 6 h, exhibited essentially no change in DPOAE levels.

show abstract

Increased Ototoxicity in Both Young and Old Mice

Cited by 65 publications

References 15 publications

Protection against Noise-Induced Hearing Loss in Young CBA/J Mice by Low-Dose Kanamycin

Protection against Noise-Induced Hearing Loss in Young CBA/J Mice by Low-Dose Kanamycin

Sox2 and Jagged1 Expression in Normal and Drug-Damaged Adult Mouse Inner Ear

Cochlear function in mice following inhalation of brevetoxin-3

Contact Info

Product

Resources

About