胆红素所致听觉系统神经损害的新机制

A new mechanism of bilirubin-induced auditory nervous system injury

严重高胆红素血症(黄疸)可导致特定神经系统的功能损害,具有神经核团选择性、新生儿期易感性等临床特征。听觉神经系统对胆红素毒性高度敏感,临床表现为最早出现的、或者是惟一显症的急性功能损害,或者是隐匿的、成年期显症的听神经病谱系障碍。临床及基础领域的零散研究表明,兴奋毒性是胆红素诱发神经功能障碍的主要途径,但听觉障碍特征及损害机制均未明确。听觉环路电信号的产生及传导,有赖于神经元动作电位的节律形成,以及电信号在神经纤维的同步化传导。适度兴奋性是维系正常听觉的基础,但"癫痫样"过度兴奋将导致细胞能量代谢紊乱,细胞内Ca2+增多,最终导致细胞凋亡或坏死。探索胆红素所致听觉神经毒性机制的研究,不仅有助于揭示听觉环路病理生理特征,也有助于揭示胆红素脑病的发生机制及拮抗措施。

Severe hyperbilirubinemia(jaundice)may lead to functional damage of a specific nervous system,presenting clinical characteristics such as nucleus selectivity and neonatal susceptibility. The auditory nervous system is extremely sensitive to bilirubin toxicity. The clinical manifestations comprise of acute functional impairment,which might be the first or only manifestation,or hidden and adult onset auditory neuropathy spectrum disorder. Scattered clinical and basic studies have shown that excitotoxicity is the main pathway of bilirubin-induced neurological dysfunction. However,the characteristics and mechanism of hearing impairment are still unknown. The generation and transmission of electrical signals in an auditory circuit depend on both the rhythmic firing of action potential of neurons and the synchronous transmission among nerve fibers. Moderate excitability is the basis of maintaining normal hearing,but"epilepsy-like"overexcitation may lead to an impairment of cell energy metabolism,increase in intracellular Ca2+,and eventual cell apoptosis or necrosis. Exploring the mechanism of bilirubin-induced auditory neurotoxicity is not only helpful in revealing the pathophysiological characteristics of auditory circuits,but also in shedding light on the pathogenesis and antagonistic measures of bilirubin encephalopathy.