A mouse model for degeneration of the spiral ligament.
Previous studies have indicated the importance of the spiral ligament (SL) in the pathogenesis of sensorineural hearing loss. The aim of this study was to establish a mouse model for SL degeneration as the basis for the development of new strategies for SL regeneration. We injected 3-nitropropionic acid (3-NP), an inhibitor of succinate dehydrogenase, at various concentrations into the posterior semicircular canal of adult C57BL/6 mice. Saline-injected animals were used as controls. Auditory function was monitored by measurements of auditory brain stem responses (ABRs). On postoperative day 14, cochlear specimens were obtained after the measurement of the endocochlear potential (EP). Animals that were injected with 5 or 10 mM 3-NP showed a massive elevation of ABR thresholds along with extensive degeneration of the cochleae. Cochleae injected with 1 mM 3-NP exhibited selective degeneration of the SL fibrocytes but alterations in EP levels and ABR thresholds were not of sufficient magnitude to allow for testing functional recovery after therapeutic interventions. Animals injected with 3 mM 3-NP showed a reduction of around 50% in the EP along with a significant loss of SL fibrocytes, although degeneration of spiral ganglion neurons and hair cells was still present in certain regions. These findings indicate that cochleae injected with 3 mM 3-NP may be useful in investigations designed to test the feasibility of new therapeutic manipulations for functional SL regeneration.
Kada
Shinpei
S
Department of Otolaryngology, Head and Neck Surgery, Graduate School of Medicine, Kyoto University, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
Nakagawa
Takayuki
T
Ito
Juichi
J
D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage; D002452:Cell Count; D003055:Cochlear Microphonic Potentials / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D005260:Female; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D009574:Nitro Compounds / Q000008:administration & dosage; D009925:Organ of Corti / Q000187:drug effects / Q000473:pathology; D011422:Propionates / Q000008:administration & dosage; D013136:Spiral Ganglion / Q000187:drug effects / Q000473:pathology; D055493:Spiral Ligament of Cochlea / Q000187:drug effects / Q000473:pathology*; D013316:Stria Vascularis / Q000187:drug effects / Q000473:pathology
D000959:Antihypertensive Agents; D009574:Nitro Compounds; D011422:Propionates; C015392:3-nitropropionic acid