A method for intracochlear drug delivery in the mouse.
The confluence of two rapidly emerging research arenas - development of mouse models of human deafness and inner ear drug therapy for treatment and prevention of hearing loss - provides an opportunity for unprecedented approaches to study and treat deafness. Toward such goals, we have developed a method for intracochlear drug delivery in the mouse. The bulla was exposed using a ventral approach and the stapedial artery cauterized. An opening made into the inferior-medial aspect of the bulla, where the basal cochlear wall fuses with tympanic bulla, provided direct access to the scala tympani without separately opening the bulla or elevating auditory response thresholds. Cochlear responses, assayed by frequency-specific effects on ABRs and DPOAEs, were stable with infusion (1 microl/h) of an artificial perilymph solution (80 min). The glutamate receptor antagonist, CNQX (100 microM; 175 min), reduced ABR responses without affecting DPOAEs. Salicylate (5mM; 165 min) altered both. Both drugs had greatest effects at high frequencies, but distributed throughout the cochlea and were reversible. The safe delivery of drugs into the cochlea by this approach has immediate application in the study and treatment of various forms of human hearing loss that can be modeled in the mouse.
Chen
Zhiqiang
Z
Department of Otology and Laryngology, Harvard Medical School, Boston, MA 02114, USA. zhiqiang-chen@meei.harvard.edu
Mikulec
Anthony A
AA
McKenna
Michael J
MJ
Sewell
William F
WF
Kujawa
Sharon G
SG
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D003051:Cochlea / Q000187:drug effects / Q000601:surgery*; D016503:Drug Delivery Systems / Q000379:methods*; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D051379:Mice; D008808:Mice, Inbred CBA; D023421:Models, Animal; D019635:Neurosurgical Procedures; D017084:Otoacoustic Emissions, Spontaneous / Q000187:drug effects; D010498:Perilymph; D012459:Salicylates / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D018691:Excitatory Amino Acid Antagonists; D012459:Salicylates; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione