Department of Otolaryngology-Head and Neck Surgery, University Hospitals Case Medical Center, Cleveland, Ohio 44106, USA.
Otol Neurotol. 2011 Dec;32(9):1583-9. doi: 10.1097/MAO.0b013e3182382a64.
Interruption of the excitotoxic and inflammatory pathways implicated in endolymphatic hydrops (ELH)-associated hearing loss (HL) should afford hearing protection at the neuronal level.
Previous work in our laboratory in the mouse model of ELH shows that dimethyl sulfoxide (DMSO), an anti-inflammatory solvent, can slow the progression of HL before neuronal degeneration occurs. Riluzole, a glutamate release inhibitor, may provide synergistic benefit. This study was designed to quantify the effects of DMSO and riluzole in a long-term model.
Guinea pigs with surgically induced ELH were sorted into 3 groups: riluzole+DMSO (Group 1), DMSO alone (Group 2), and untreated controls (Group 3). Animals in Groups 1 and 2 received daily injections of the study drug(s). All animals underwent auditory-evoked brainstem response evaluation every 4 weeks until 24 weeks, when they were sacrificed. Cochleae were preserved; spiral ganglion density was quantified. Animals without hydrops were excluded from the study as surgical failures.
Animals from all groups developed unilateral HL. At the end of the experiment, HL was significantly lower in Group 1 relative to Group 3 (p = 0.049) and trended toward lower in Group 2 relative to Group 3 (p = 0.097). Groups 1 and 2 were not different (p = 0.311). At the cellular level, there is no evidence of neuronal degeneration in either treated group, whereas there is a significant neuronal degeneration in the untreated group.
These results confirm the hearing protection observed with DMSO in short-term studies. However, unlike the previous study, which showed no additive benefit to riluzole, the combined treatment group in this study showed a hearing-protective effect at 24 weeks. This indicates a potential additive benefit conferred by riluzole toward long-term hearing protection. The study also finds evidence of statistically significant neuronal protection with both treatment groups. Overall, study provides additional evidence that DMSO and riluzole may preserve or slow the long-term progression of ELH-associated HL.
中断与内淋巴积水（ELH）相关听力损失（HL）相关的兴奋性毒性和炎症途径，应该可以在神经元水平提供听力保护。
我们实验室之前在 ELH 的小鼠模型中的工作表明，二甲基亚砜（DMSO），一种抗炎溶剂，可以在神经元变性发生之前减缓 HL 的进展。利鲁唑，一种谷氨酸释放抑制剂，可能会提供协同益处。这项研究旨在量化 DMSO 和利鲁唑在长期模型中的作用。
患有手术诱导的 ELH 的豚鼠被分为 3 组：利鲁唑+DMSO（第 1 组）、DMSO 单独（第 2 组）和未治疗的对照组（第 3 组）。第 1 组和第 2 组动物每天接受研究药物注射。所有动物在 24 周时进行听觉诱发电位脑干反应评估，然后处死。耳蜗被保存；螺旋神经节密度被量化。由于手术失败，没有 ELH 的动物被排除在研究之外。
所有组的动物均出现单侧 HL。在实验结束时，与第 3 组相比，第 1 组的 HL 明显降低（p = 0.049），第 2 组与第 3 组相比 HL 也有降低趋势（p = 0.097）。第 1 组和第 2 组之间没有差异（p = 0.311）。在细胞水平上，治疗组均没有神经元变性的证据，而未治疗组则存在明显的神经元变性。
这些结果证实了 DMSO 在短期研究中观察到的听力保护作用。然而，与之前的研究不同，该研究没有显示利鲁唑有额外的益处，本研究中的联合治疗组在 24 周时显示出听力保护作用。这表明利鲁唑可能对长期听力保护具有潜在的附加益处。该研究还发现了两种治疗组在统计学上都有显著的神经元保护作用的证据。总体而言，该研究提供了额外的证据表明 DMSO 和利鲁唑可能会保护或减缓 ELH 相关 HL 的长期进展。
