AMPA/kainate-type glutamate receptor antagonist reduces progressive inner hair cell loss after transient cochlear ischemia.
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.
Hakuba
Nobuhiro
N
Department of Otolaryngology, Ehime University School of Medicine, Shigenobu-cho, Onsen-gun, 791-0295, Ehime, Japan. hakubax@m.ehime-u.ac.jp
Matsubara
Atsushi
A
Hyodo
Jun
J
Taniguchi
Masafumi
M
Maetani
Toshiki
T
Shimizu
Yoshitaka
Y
Tsujiuchi
Yuko
Y
Shudou
Masachika
M
Gyo
Kiyofumi
K
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
D018691:Excitatory Amino Acid Antagonists; D011810:Quinoxalines; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; C056723:FG 9041; D016291:Dizocilpine Maleate