卡铂对灰鼠中枢听觉系统影响研究

EFFECT OF CARBOPLATIN ON THE CENTRAL AUDITORY SYSTEM IN THE CHINCHILLA

目的:卡铂选择性破坏灰鼠的内毛细胞和I型传入神经末梢已被人们所证实,但是,卡铂是否损害耳蜗核、下丘和听觉皮层还不清楚,本文旨在为了观察卡铂对灰鼠听觉中枢的毒性作用。方法:采用恒低温冷冻连续脑组织切片,以中枢听觉系统神经元的密度来评价卡铂对灰鼠中枢听觉系统的影响。结果:发现注射卡铂3和4周后,耳蜗背侧核和腹侧核神经元数量明显的减少,与正常动物比较有显著性差异(P< 0.001)。而下丘和听觉皮层神经元的变化与正常灰鼠比较无明显差异。结论:注射卡铂3和4周后对灰鼠耳蜗核有明显的毒性作用,可引起耳蜗核神经元数量明显的减少,但是,对下丘和听皮层未见明显毒性损伤。

Aim:Carboplatin selectively destroys inner hair cells and type I spiral ganglion neurons in the chinchilla cochlea, however, its effects on the central auditory system are largely unknown. The aim of this study was to determine if carboplatin treatment affects neuron survival in the cochlear nucleus (CN), inferior colliculus (IC) or auditory cortex (AC) of the chinchilla. Methods: Chinchillas were treated with carboplatin (100 mg/kg IP). Three and four weeks later, they were sacrificed and perfused intracardially with fixative. Surface preparations of the Corti抯 organ were analyzed for hair cell loss. Serial frozen sections taken from the CN, IC and AC were stained with toluidine blue, and the number of neurons were counted in representative sections from control and carboplatin-treated chinchillas. Results:The results showed that carboplatin destroyed approximately 80% of the inner hair cells in the cochlea. In the central auditory system, carboplatin resulted in a significant loss of neurons in the anteroventral, posteroventral and dorsal divisions of the CN, but not in the IC or AC. Conclusions:Effect of carboplatin on the CN in the chinchilla is evident ototoxicity, but the carboplatin do not cause ototoxicity in the IC or AC. Future studies will determine if the loss of neurons in the CN is a direct result of carboplatin neurotoxicity, or a secondary effect of inner hair cell and spiral ganglion neuron loss in the auditory periphery.