Deafness Induction in Mice

Jansen, Thijs; Bremer, Hendrik G; Topsakal, Vedat; Hendriksen, Ferry G. J.; Klis, Sjaak F.L.; Grolman, Wilko

doi:10.1097/mao.0b013e318291c610

Cited by 21 publications

(28 citation statements)

References 24 publications

(41 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This species difference is thought to be caused by a difference in pharmacokinetics of aminoglycosides, rather than a resilience of the hair cells to degenerate when aminoglycosides are present (Wu et al, 2002). Indeed, when mice are injected with a combination of kanamycin and furosemide, which opens the blood-brain barrier and reduces renal clearance, aminoglycoside ototoxicity is more severe (Jansen et al, 2013). This suggests that kanamycin applied directly in the cochlea, as carried out in the current study, would be as effective in mice as in guinea pig (Zeng et al, 2009, Zeng et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Altered vesicular glutamate transporter distributions in the mouse cochlear nucleus following cochlear insult

et al. 2016

View full text Add to dashboard Cite

Vesicular glutamate transporters 1 and 2 (VGLUT1 and VGLUT2) have distinct distributions in the cochlear nucleus that correspond to the sources of the labeled terminals. VGLUT1 is mainly associated with terminals of auditory nerve fibers, whereas VGLUT2 is mainly associated with glutamatergic terminals deriving from other sources that project to the cochlear nucleus (CN), including somatosensory and vestibular terminals. Previous studies in guinea pig have shown that cochlear damage results in a decrease of VGLUT1-labeled puncta and an increase in VGLUT2-labeled puncta. This indicates cross-modal compensation that is of potential importance in somatic tinnitus. To examine whether this effect is consistent across species and to provide a background for future studies, using transgenesis, the current study examines VGLUT expression profiles upon cochlear insult by intracochlear kanamycin injections in the mouse. Intracochlear kanamycin injections abolished ipsilateral ABR responses in all animals and reduced ipsilateral spiral ganglion neuron densities in animals that were sacrificed after four weeks, but not in animals that were sacrificed after three weeks. In all unilaterally deafened animals, VGLUT1 density was decreased in CN regions that receive auditory nerve fiber terminals, i.e. in the deep layer of the dorsal cochlear nucleus (DCN), in the interstitial region where the auditory nerve enters the CN, and in the magnocellular region of the antero- and posteroventral CN. In contrast, density of VGLUT2 expression was upregulated in the fusiform cell layer of the DCN and in the granule cell lamina, which are known to receive somatosensory and vestibular terminals. These results show that a cochlear insult induces cross-modal compensation in the cochlear nucleus of the mouse, confirming previous findings in guinea pig, and that these changes are not dependent on the occurrence of spiral ganglion neuron degeneration.

show abstract

Section: Discussionmentioning

confidence: 99%

Altered vesicular glutamate transporter distributions in the mouse cochlear nucleus following cochlear insult

et al. 2016

View full text Add to dashboard Cite

show abstract

“…The present study included cochleae obtained from 6–8 weeks old C57BL/6JOlaHsd male mice previously described by Jansen et al (). The study included two experimental groups and a group of four nondeafened mice as controls.…”

Section: Methodsmentioning

confidence: 99%

“…In the first experimental group, 11 mice received a subcutaneous injection with kanamycin sulfate (Sigma‐Aldrich) at a concentration of 700 mg/kg and an intravenous tail vein injection with furosemide (Centrafarm, 100 mg/kg) (Jansen et al, ). Eight of these mice showed significant ABR threshold shifts (59 ± 4.5 dB; P ≤ 0.001), while the three remaining mice did not respond to the treatment and showed similar thresholds to the control group.…”

Section: Methodsmentioning

confidence: 99%

“…In the second experimental group, mice received a subcutaneous injection with 1,000 mg/kg kanamycin sulfate and an intravenous tail vein injection with 100 mg/kg furosemide (Jansen et al, ). Nine of the 12 treated mice showed significant ABR threshold shifts (59 ± 2.9 dB; P ≤ 0.001), while the three remaining mice from this group did not respond to the treatment.…”

Section: Methodsmentioning

confidence: 99%

“…Animal models of sensorineural hearing loss are essential to develop different strategies aiming at hearing restoration. Our group has recently evidenced that a single high‐dose kanamycin injection followed by an intravenous furosemide delivery causes severe auditory brainstem response (ABR) threshold shifts, auditory hair cell destruction, and a loss of spiral ganglion cells in mice (Jansen et al, ).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Scar formation in mice deafened with kanamycin and furosemide

Żak

Linden

Bezdjian

et al. 2016

Microscopy Res & Technique

Self Cite

View full text Add to dashboard Cite

In mammals, hair cell loss is irreversible and leads to hearing loss. To develop and test the functioning of different strategies aiming at hair cell regeneration, animal models of sensorineural hearing loss are essential. Although cochleae of these animals should lack hair cells, supporting cells should be preserved forming an environment for the regenerated hair cells. In this study, we investigated how ototoxic treatment with kanamycin and furosemide changes the structure of cochlear sensory epithelium in mice. The study also compared different tissue preparation protocols for scanning electron microscopy (SEM). Cochleae were collected from deafened and nondeafened mice and further processed for plastic mid modiolar sections and SEM. For comparing SEM protocols, cochleae from nondeafened mice were processed using three protocols: osmium-thiocarbohydrazide-osmium (OTO), tannic acid-arginine-osmium, and the conventional method with gold-coating. The OTO method demonstrated optimal cochlear tissue preservation. Histological investigation of cochleae of deafened mice revealed that the supporting cells enlarged and ultimately replaced the lost hair cells forming types 1 and 2 phalangeal scars in a base towards apex gradient. The type 3 epithelial scar, flattened epithelium, has not been seen in analysed cochleae. The study concluded that mice deafened with kanamycin and furosemide formed scars containing supporting cells, which renders this mouse model suitable for testing various hair cell regeneration approaches. Microsc. Res. Tech. 79:766-772, 2016. © 2016 Wiley Periodicals, Inc.

show abstract