Hyodo Jun, Hakuba Nobuhiro, Hato Naohito, Takeda Shoichirou, Okada Masahiro, Omotehara Yoshinori, Gyo Kiyofumi
Department of Otolaryngology, Ehime University School of Medicine, Ehime 791-0295, Japan.
Neuroreport. 2009 Sep 23;20(14):1255-9. doi: 10.1097/WNR.0b013e32833017ce.
Glutamate neurotoxicity in cochlear hair cells was investigated by administering the glutamate agonist alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) into the scala tympani of Mongolian gerbils. AMPA administration caused the formation of large number of vacuoles in the inner hair cells (IHCs) and dendritic terminals. The number of degenerated hair cells was counted using rhodamine-phalloidin and Hoechst 33342 staining. The administration of 50 microM AMPA caused reversible elevation of the auditory brainstem response threshold without loss of IHCs. In contrast, 200 microM AMPA induced a substantial elevation of the auditory brainstem response threshold with the characteristic disappearance of IHCs. As cochlear ischemia involves excessive glutamate release, these results suggest that an elevated glutamate level in the cochlea is responsible for the progressive IHC death related to ischemic injury.
通过向蒙古沙鼠的鼓阶内注射谷氨酸激动剂α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA），研究了谷氨酸对耳蜗毛细胞的神经毒性。注射AMPA导致内毛细胞（IHC）和树突末端形成大量空泡。使用罗丹明-鬼笔环肽和Hoechst 33342染色对退化毛细胞的数量进行计数。注射50微摩尔/升的AMPA导致听觉脑干反应阈值可逆性升高，而内毛细胞未损失。相比之下，注射200微摩尔/升的AMPA导致听觉脑干反应阈值大幅升高，同时内毛细胞出现特征性消失。由于耳蜗缺血涉及谷氨酸的过度释放，这些结果表明，耳蜗中谷氨酸水平升高是导致与缺血性损伤相关的内毛细胞进行性死亡的原因。
