Pujol R, Rebillard G, Puel J L, Lenoir M, Eybalin M, Recasens M
INSERM-U. 254, Laboratoire de Neurobiologie de l'Audition, Hopital St. Charles, Montpellier, France.
Acta Otolaryngol Suppl. 1990;476:32-6. doi: 10.3109/00016489109127253.
Glutamate is considered to be one of the most common neurotransmitters in the fast excitatory synapses in the central nervous system. On the other hand, its excitotoxic properties are increasingly cited to explain some of the brain damage linked with hypoxia and ischaemia: i.e., those that occur frequently in ageing. An excess release of glutamate could, either directly or indirectly, activate receptors on the postsynaptic neuron, causing ion influxes accompanied by a massive entry of water, which would lead to an acute swelling of dendrites. In addition, calcium influx deregulates calcium homeostasis, which could lead to cell death. In the cochlea, glutamate is now considered to be one of the best candidates to mediate neurotransmission between inner hair cells (IHCs) and the auditory nerve dendrites. Among the variety of anatomical and physiological findings supporting the glutamate hypothesis, is the striking similarity of acute damage in the organ of Corti caused by exposure to a glutamate analogue (kainic acid), or by hypoxia, or even by an intense loud noise. In all cases an immediate swelling is observed, specifically affecting the radial afferents below the IHCs. The best explanation for this swelling is related to glutamate (or glutamate analogue) excitotoxicity. Thus, some of the cochlear damage that occur with ageing, especially the loss of the radial afferent fibres and type I ganglion cells, might well be attributed to glutamate excitotoxicity linked to vascular atrophy. The present paper discusses this hypothesis.
谷氨酸被认为是中枢神经系统快速兴奋性突触中最常见的神经递质之一。另一方面，其兴奋性毒性特性越来越多地被引用来解释一些与缺氧和缺血相关的脑损伤，即那些在衰老过程中经常发生的损伤。谷氨酸的过量释放可能直接或间接激活突触后神经元上的受体，导致离子内流并伴有大量水分进入，这将导致树突急性肿胀。此外，钙内流会破坏钙稳态，从而可能导致细胞死亡。在耳蜗中，谷氨酸现在被认为是介导内毛细胞（IHC）与听神经树突之间神经传递的最佳候选者之一。在支持谷氨酸假说的各种解剖学和生理学发现中，有一个显著的相似之处，即暴露于谷氨酸类似物（红藻氨酸）、缺氧甚至强烈噪音所导致的柯蒂氏器急性损伤。在所有这些情况下，都观察到立即肿胀，特别影响内毛细胞下方的放射状传入纤维。对这种肿胀的最佳解释与谷氨酸（或谷氨酸类似物）的兴奋性毒性有关。因此，衰老过程中发生的一些耳蜗损伤，尤其是放射状传入纤维和I型神经节细胞的丧失，很可能归因于与血管萎缩相关的谷氨酸兴奋性毒性。本文讨论了这一假说。
