Study on Role of Glutamate and its Protection of Neural Toxity in Inner Ear Damage

谷氨酸是初级传入听觉神经元突触上的一种神经递质。当内耳受损时，它会过度释放到周围环境中，对周围环境产生毒性，从而加重听力损失。在第一个实验中，我们研究了沙鼠短暂性耳蜗缺血导致听力损失的机制。结果表明，耳蜗缺血5min可引起内毛细胞迟发性死亡，这可能与谷氨酸的兴奋性毒性有关。这与淋巴周围谷氨酸浓度显著增加有关。在第二个实验中，研究了低温对沙鼠耳蜗缺血15分钟的影响。低温治疗对预防耳蜗缺氧引起的听力损失非常有效。与常温组相比，低温组毛细胞的损失很少。在第三个实验中，研究了谷氨酸在谷氨酸转运体GLAST基因缺失小鼠噪声性听力损失中的作用。在缺乏GLAST的小鼠中，持续暴露于大噪声导致的听力损失大于野生小鼠。由于GLAST在突触空间吸收谷氨酸，因此初级传入听觉神经元突触中谷氨酸的代谢对防止噪声引起的听力损失至关重要。

Glutamate is a neurotransmitter at the synapse of the primary afferent auditory neuron. When the inner ear is damaged, it is released excessively to the surroundings and aggravates hearing loss by working toxic to them. In the first experiment, we investigated the mechanisms of hearing loss due to transient cochlear ischemia in gerbils. The results showed that cochlear ischemia for 5 min causes delayed neuronal death of the inner hair cells probably due to excitotoxicity of glutamate. This was supported by remarkable increase of glutamate concentration in the perilymph. In the second experiment, effects of hypothermia were investigated in gerbils with cochlear ischemia for 15 min. Hypothermia was very effective to prevent hearing loss due to cochlear anoxia. Loss of the hair cells in hyopthermic group was very few compared to those in normothermic group. In the third experiment, role of glutamate in noise induced hearing loss was studied in mouse which genetically lacks GLAST, a glutamate transporter. In GLAST lacking mouse, hearing loss due to continuous exposure to loud noise was greater than that in wild mouse. As GLAST resorbs glutamate in the synaptic space, metabolism of glutamate in the synapse of the primary afferent auditory neuron is important to prevent hearing loss by noise.