Maruyama Jun, Yamagata Takahiko, Ulfendahl Mats, Bredberg Göran, Altschuler Richard A, Miller Josef M
Center for Hearing and Communication Research, Karolinska Institutet, and Department of Otolaryngology, Karolinska University Hospital, Solna, Stockholm, Sweden.
Neurobiol Dis. 2007 Feb;25(2):309-18. doi: 10.1016/j.nbd.2006.09.012. Epub 2006 Nov 16.
Based on in vitro studies, it is hypothesized that neurotrophic factor deprivation following deafferentation elicits an oxidative state change in the deafferented neuron and the formation of free radicals that then signal cell death pathways. This pathway to cell death was tested in vivo by assessing the efficacy of antioxidants (AOs) to prevent degeneration of deafferented CNVIII spiral ganglion cells (SGCs) in deafened guinea pigs. Following destruction of sensory cells, guinea pigs were treated immediately with Trolox (a water soluble vitamin E analogue)+ascorbic acid (vitamin C) administered either locally, directly in the inner ear, or systemically. Electrical auditory brainstem response (EABR) thresholds were recorded to assess nerve function and showed a large increase following deafness. In treated animals EABR thresholds decreased and surviving SGCs were increased significantly compared to untreated animals. These results indicate that a change in oxidative state following deafferentation plays a role in nerve cell death and antioxidant therapy may rescue SGCs from deafferentation-induced degeneration.
基于体外研究，推测去传入神经支配后神经营养因子缺乏会引发去传入神经的神经元氧化状态改变并形成自由基，进而激活细胞死亡信号通路。通过评估抗氧化剂（AO）预防耳聋豚鼠去传入神经支配的第八对脑神经螺旋神经节细胞（SGC）退变的效果，在体内对这条细胞死亡途径进行了测试。在感觉细胞被破坏后，立即对豚鼠进行局部（直接在内耳）或全身给予生育三烯酚（一种水溶性维生素E类似物）+抗坏血酸（维生素C）的治疗。记录电听觉脑干反应（EABR）阈值以评估神经功能，结果显示耳聋后阈值大幅升高。与未治疗的动物相比，治疗动物的EABR阈值降低，存活的SGC数量显著增加。这些结果表明，去传入神经支配后氧化状态的改变在神经细胞死亡中起作用，抗氧化治疗可能使SGC免受去传入神经支配诱导的退变。
