Labyrinthine Barriers and Cochlear Homeostasis

Juhn, Steven K.; Rybak, Leonard P.

doi:10.3109/00016488109138538

Cited by 151 publications

(86 citation statements)

References 7 publications

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“…Direct delivery to the fluids of the inner ear is necessary because of the presence of a blood-labyrinth drug barrier, which is anatomically and functionally similar to the blood-brain barrier [20,21]. Direct delivery also has significant potential advantages for therapeutic application.…”

Section: Discussionmentioning

confidence: 99%

Development of a Microfluidics-Based Intracochlear Drug Delivery Device

et al. 2009

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Background: Direct delivery of drugs and other agents into the inner ear will be important for many emerging therapies, including the treatment of degenerative disorders and guiding regeneration. Methods: We have taken a microfluidics/MEMS (MicroElectroMechanical Systems) technology approach to develop a fully implantable reciprocating inner-ear drug-delivery system capable of timed and sequenced delivery of agents directly into perilymph of the cochlea. Iterations of the device were tested in guinea pigs to determine the flow characteristics required for safe and effective delivery. For these tests, we used the glutamate receptor blocker DNQX, which alters auditory nerve responses but not cochlear distortion product otoacoustic emissions. Results: We have demonstrated safe and effective delivery of agents into the scala tympani. Equilibration of the drug in the basal turn occurs rapidly (within tens of minutes) and is dependent on reciprocating flow parameters. Conclusion: We have described a prototype system for the direct delivery of drugs to the inner ear that has the potential to be a fully implantable means for safe and effective treatment of hearing loss and other diseases.

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Section: Discussionmentioning

confidence: 99%

Development of a Microfluidics-Based Intracochlear Drug Delivery Device

et al. 2009

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“…Direct delivery to the fluids of the inner ear is necessary because of the presence of a bloodlabyrinth drug barrier, which is anatomically and functionally similar to the blood-brain barrier [19,20]. Direct delivery also has significant potential advantages for therapeutic application.…”

Section: Introductionmentioning

confidence: 99%

Inner ear drug delivery via a reciprocating perfusion system in the guinea pig

Chen

Kujawa

McKenna

et al. 2005

Journal of Controlled Release

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Rapid progress in understanding the molecular mechanisms associated with cochlear and auditory nerve degenerative processes offers hope for the development of gene-transfer and molecular approaches to treat these diseases in patients. For therapies based on these discoveries to become clinically useful, it will be necessary to develop safe and reliable mechanisms for the delivery of drugs into the inner ear, bypassing the blood-labyrinthine barrier. Toward the goal of developing an inner ear perfusion device for human use, a reciprocating microfluidic system that allows perfusion of drugs into the cochlear perilymph through a single inlet hole in scala tympani of the basal turn was developed. The performance of a prototype, extracorporeal reciprocating perfusion system in guinea pigs is described. Analysis of the cochlear distribution of compounds after perfusion took advantage of the place-dependent generation of responses to tones along the length of the cochlea. Perfusion with a control artificial perilymph solution had no effect. Two drugs with wellcharacterized effects on cochlear physiology, salicylate (5 mM) and DNQX (6,7-Dinitroquinoxaline-2,3-dione; 100 and 300 μM), reversibly altered responses. The magnitude of drug effect decreased with distance from the perfusion pipette for up to 10 mm, and increased with dose and length of application.

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“…Noise-triggered damage leads to impairment of the stereocilias of the hair cells, the loss of hair cells, and structural distortion at the spiral ligament and spiral ganglion [2,3] . It was reported that hair cells become dysfunctional within 2 weeks after noise exposure, and an edema develops in the spiral ganglion neurons [4,5] . Nevertheless, the molecular mechanisms of noise-induced hearing loss are still not fully understood.…”

Section: Introductionmentioning

confidence: 99%