title: AMPA/kainate-type glutamate receptor antagonist reduces progressive inner hair cell loss after transient cochlear ischemia.
abstract: We investigated the effect of glutamate receptor antagonists on progressive inner hair cell (IHC) loss following transient cochlear ischemia in gerbils. Transient cochlear ischemia was induced by 15-min bilateral vertebral artery occlusion. An alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)/kainate-type glutamate receptor antagonist, 6-7-dinitroquinoxaline-2,3-dione (DNQX), or an N-methyl-D-aspartate (NMDA)-type receptor antagonist, MK-801, was administered 10 min before the ischemic insult. Hearing was assessed by sequentially recording compound action potentials (CAPs) before, during, and after the ischemia. The degree of hair cell loss in the organ of Corti was evaluated in specimens stained with rhodamine-phalloidin and Hoechst 33342. On the seventh day after ischemia, the increases in the CAP threshold and the progressive IHC loss were significantly reduced in cochleae treated with DNQX, while MK-801 was ineffective. These results suggest that the AMPA receptor plays a critical role in the development of the progressive IHC loss induced by ischemia/reperfusion injury in the cochlea.
authors.affiliation: Department of Otolaryngology, Ehime University School of Medicine, Shigenobu-cho, Onsen-gun, 791-0295, Ehime, Japan. hakubax@m.ehime-u.ac.jp
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Hakuba
authors.forename: Atsushi
authors.initials: A
authors.lastname: Matsubara
authors.forename: Jun
authors.initials: J
authors.lastname: Hyodo
authors.forename: Masafumi
authors.initials: M
authors.lastname: Taniguchi
authors.forename: Toshiki
authors.initials: T
authors.lastname: Maetani
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Shimizu
authors.forename: Yuko
authors.initials: Y
authors.lastname: Tsujiuchi
authors.forename: Masachika
authors.initials: M
authors.lastname: Shudou
authors.forename: Kiyofumi
authors.initials: K
authors.lastname: Gyo
mesh_terms: D000161:Acoustic Stimulation; D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D003051:Cochlea / Q000098:blood supply / Q000473:pathology* / Q000648:ultrastructure; D003056:Cochlear Nerve / Q000187:drug effects / Q000648:ultrastructure; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005849:Gerbillinae; D006199:Hair Cells, Auditory, Inner / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D006309:Hearing / Q000187:drug effects; D007150:Immunohistochemistry; D007511:Ischemia / Q000188:drug therapy; D008297:Male; D008854:Microscopy, Electron; D011810:Quinoxalines / Q000494:pharmacology; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors* / Q000648:ultrastructure; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000648:ultrastructure; D013569:Synapses / Q000187:drug effects / Q000648:ultrastructure
chemical_list: D018691:Excitatory Amino Acid Antagonists; D011810:Quinoxalines; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; C056723:FG 9041; D016291:Dizocilpine Maleate