Prophylactic and therapeutic functions of T-type calcium blockers against noise-induced hearing loss
Prophylactic and therapeutic functions of T-type calcium blockers against noise-induced hearing loss
复制标题
DOI：
10.1016/j.heares.2006.12.011
复制
发表时间：
2007-04-01
期刊：
影响因子：
2.8
通讯作者：
Bao, Jianxin
中科院分区：
文献类型：
--
作者：
Shen, Haiyan;Zhang, Baoping;Bao, Jianxin
Cochlear noise injury is the second most frequent cause of sensorineural hearing loss, after aging. Because calcium dysregulation is a widely recognized contributor to noise injury, we examined the potential of calcium channel blockers to reduce noise-induced hearing loss (NIHL) in mice. We focused on two T-type calcium blockers, trimethadione and ethosuximide, which are anti-epileptics approved by the Food and Drug Administration. Young C57BL/6 mice of either gender were divided into three groups: a 'prevention' group receiving the blocker via drinking water before noise exposure; a 'treatment' group receiving the blocker via drinking water after noise exposure; and controls receiving noise alone. Trimethadione significantly reduced NIHL when applied before noise exposure, as determined by auditory brainstem recording. Both ethosuximide and trimethadione were effective in reducing NIHL when applied after noise exposure. Results were influenced by gender, with males generally receiving greater benefit than females. Quantitation of hair cell and neuronal density suggested that preservation of outer hair cells could account for the observed protection. Immunocytochemistry and RT-PCR suggested that this protection involves direct action of T-type blockers on al subunits comprising one or more Ca,3 calcium channel types in the cochlea. Our findings provide a basis for clinical studies testing T-type calcium blockers both to prevent and treat NIHL. (C) 2007 Elsevier B.V. All rights reserved.
