Ouabain에 의해 유도된 선택적 나선신경절 세포손상 = Damage of Spiral Ganglion Cell Induced by Ouabain Application in Cat

다국어 초록 (Multilingual Abstract)

Background and Objectives Auditory neuropathy is a hearing disorder characterized by the absence or the marked impairment of the auditory brainstem responses with the preservation of the cochlear microphonics (CMs) and otoacoustic emissions. This suggests that outer hair cell (OHC) function is normal but proximal auditory function to OHCs is impaired. It is assumed that the lesion is localized at the level of the inner hair cells (IHCs), auditory nerve fibers, or the synapse between them. This study was aimed to observe the change of hearing threshold and pathology of spiral ganglion cell induced by ouabain application, and present basic data to explain the auditory neuropathy.
Materials and Method Twenty ears of twenty normal hearing cats were used in this study. Cats were treated with 100 μL ouabain (1 mM) applied on the round window. After three days, compound action potential (CAP) and CM were measured and the cochlea was obtained. Pathologic change of spiral ganglion cell was evaluated under light microscope after H&E stain. Normal saline was injected for the control group.
Results In the ouabain group, CAP threshold was increased in all tested frequencies (p＜ 0.001) and the difference of CM threshold was not significant in all frequencies (p＞0.05). There was significant difference between CAP and CM threshold shift (p＜0.001). In the control group, there was no significant difference in CAP and CM thresholds. Light microscopic findings show that the condensed chromatin and nuclear fragments of spiral ganglion cells of an ear was exposed to ouabain, and outer hair cell and inner hair cell were not damaged.
Conclusion This study shows that the CAP threshold was significantly increased but the CM threshold was not changed in the ouabain group. Ouabain induced damage of spiral ganglion cells. This study is not sufficient to explain auditory neuropathy because threshold shift of CAP is not obvious, but it would be helpful to explain that selective damage of spiral ganglion cell would be the mechanism of auditory neuropathy.
Korean J Otorhinolaryngol-Head Neck Surg 2014;57(9):589-95

참고문헌 (Reference)

• 1 김리석, "청각신경병증 3예" 대한이비인후과학회 46 (46): 847-881, 2003
• 2 Schmiedt RA, "Ouabain application to the round window of the gerbil cochlea: a model of auditory neuropathy and apoptosis" 3 (3): 223-233, 2002
• 3 Erichsen S, "Na,K-ATPase alpha- and beta-isoforms in the developing cochlea of the mouse" 100 (100): 143-149, 1996
• 4 Lingrel JB, "Na+,K(+)-ATPase" 269 (269): 19659-19662, 1994
• 5 Hamada M, "Morphological changes induced by administration of a Na+,K+-ATPase inhibitor in normal and hydropic inner ears of the guinea pig" 119 (119): 778-786, 1999
• 6 Lingrel JB, "Ligand binding sites of Na,K-ATPase" 643 : 69-77, 1998
• 7 Heffner RS, "Hearing range of the domestic cat" 19 (19): 85-88, 1958
• 8 Hara Y, "Expression of sodium pump activities in BALB/c 3T3 cells transfected with cDNA encoding alpha 3-subunits of rat brain Na+,K+-ATPase" 238 (238): 27-30, 1988
• 9 Zuo J, "Expression of Na, K-ATPase alpha and beta isoforms in the neonatal rat cochlea" 115 (115): 497-503, 1995
• 10 Santarelli R, "Electrocochleography in auditory neuropathy" 170 (170): 32-47, 2002
• 11 Rybak LP, "Effects of topical sodium potassium ATPase inhibitors upon endocochlear potential in chinchilla" 90 (90): 808-813, 1982
• 12 Konishi T, "Effect of ouabain on cochlear potentials and endolymph composition in guinea pigs" 69 (69): 192-199, 1970
• 13 Starr A, "Cochlear receptor (microphonic and summating potentials, otoacoustic emissions) and auditory pathway (auditory brain stem potentials)activity in auditory neuropathy" 22 (22): 91-99, 2001
• 14 Rance G, "Clinical findings for a group of infants and young children with auditory neuropathy" 20 (20): 238-252, 1999
• 15 Neff WD, "Auditory thresholds of the cat" 27 : 480-483, 1955
• 16 Deltenre P, "Auditory neuropathy with preserved cochlear microphonics and secondary loss of otoacoustic emissions" 38 (38): 187-195, 1999
• 17 Starr A, "Auditory neuropathy" 119 (119): 741-753, 1996
• 18 Harrison RV, "An animal model of auditory neuropathy" 19 (19): 355-361, 1998