AMPA/kainate-type glutamate receptor antagonist reduces progressive inner hair cell loss after transient cochlear ischemia

• Published in: Brain research Vol. 979; no. 1; pp. 194 - 202
• Main Authors: Hakuba, Nobuhiro, Matsubara, Atsushi, Hyodo, Jun, Taniguchi, Masafumi, Maetani, Toshiki, Shimizu, Yoshitaka, Tsujiuchi, Yuko, Shudou, Masachika, Gyo, Kiyofumi
• Format: Journal Article
• Language: English
• Published: London Elsevier B.V 25.07.2003; Amsterdam Elsevier; New York, NY
• Subjects: Acoustic Stimulation; Action Potentials - drug effects; AMPA/kainate-type glutamate receptor; Animals; Biological and medical sciences; Cochlea - blood supply; Cochlea - pathology; Cochlea - ultrastructure; Cochlear ischemia; Cochlear Nerve - drug effects; Cochlear Nerve - ultrastructure; Compound action potential; Dizocilpine Maleate - pharmacology; DNQX; Ear, auditive nerve, cochleovestibular tract, facial nerve: diseases, semeiology; Excitatory Amino Acid Antagonists - pharmacology; Gerbillinae; Hair Cells, Auditory, Inner - drug effects; Hair Cells, Auditory, Inner - pathology; Hair Cells, Auditory, Inner - ultrastructure; Hearing - drug effects; Immunohistochemistry; Inner hair cell; Ischemia - drug therapy; Male; Medical sciences; Meriones unguiculatus; Microscopy, Electron; Non tumoral diseases; organ of Corti; Otorhinolaryngology. Stomatology; Quinoxalines - pharmacology; Receptors, AMPA - antagonists & inhibitors; Receptors, AMPA - ultrastructure; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors; Receptors, N-Methyl-D-Aspartate - ultrastructure; Synapses - drug effects; Synapses - ultrastructure; Inner hair cell; DNQX; Compound action potential; Development and regeneration; Cochlear ischemia; AMPA/kainate-type glutamate receptor; Internal ear disease; Rodentia; Cardiovascular disease; Glutamate receptor; Transitory; Kainate receptor; DNQX: Compound action potential; Vascular disease; Vertebrata; Experimental disease; AMPA receptor; Mammalia; Ischemia; Animal; Cochlea; Antagonist; Gerbil
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/S0006-8993(03)02919-6

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.