Hearing preservation in Guinea pigs with long-standing endolymphatic hydrops.
Hearing preservation in Guinea pigs with long-standing endolymphatic hydrops.
复制标题
DOI：
10.1097/mao.0b013e3182382a64
复制
发表时间：
2011-12
期刊：
影响因子：
--
通讯作者：
Megerian CA
中科院分区：
文献类型：
--
作者：
Momin SR;Melki SJ;Obokhare JO;Fares SA;Semaan MT;Megerian CA
内淋巴积水（ELH）相关性听力损失（HL）中涉及的兴奋性毒性和炎症通路的中断应在神经元水平上提供听力保护。我们实验室先前在ELH小鼠模型中的工作表明，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。阿曲唑，谷氨酸释放抑制剂，可以提供协同效益。本研究旨在量化DMSO和利鲁唑在长期模型中的作用。将具有药物诱导的ELH的豚鼠分为三组：利鲁唑+DMSO（G1）、DMSO单独（G2）和未处理对照（G3）。第1组和第2组动物每日接受研究药物注射。所有动物每4周进行一次ABR评价，直至24周处死。保留耳蜗;定量螺旋神经节密度。无积液的动物因手术失败而从研究中排除。所有组的动物均发生单侧HL。在实验结束时，第1组的HL显著低于第3组（p=0.049），第2组的HL有降低趋势（p=0.097），第1组和第2组无差异（p=0.311）。在细胞水平上，两个给药组中均无神经元变性的证据，而未给药组中存在显著的神经元变性。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，与先前的研究显示利鲁唑没有额外的益处不同，本研究中的联合治疗组在24周时显示出听力保护作用。这表明利鲁唑对长期听力保护具有潜在的附加益处。该研究还发现了两个治疗组具有显著神经元保护作用的证据。总体而言，研究提供了额外的证据，证明DMSO和利鲁唑可维持或减缓ELH相关HL的长期进展。
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 lab in the mouse model of ELH shows that 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 three groups: riluzole+DMSO (G1), DMSO alone (G2) and untreated controls (G3). Animals in Groups 1 and 2 received daily injections of the study drug(s). All animals underwent ABR 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, while there is 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.