The University of Sydney, Meniere's Research Laboratory, Australia.
The University of Sydney, Meniere's Research Laboratory, Australia.
Hear Res. 2018 Dec;370:105-112. doi: 10.1016/j.heares.2018.10.007. Epub 2018 Oct 17.
In an attempt to develop an animal model of immune mediated Meniere's disease, we have injected lipopolysaccharide (LPS) directly into scala media of guinea pigs and monitored functional and morphological changes over a period of 6 weeks. Depending on the concentration of LPS, changes ranged from moderate-to-severe hearing loss and endolymphatic hydrops with minimal cellular infiltrate or fibrosis, to dense cellular infiltration that filled the scalae. Interestingly, higher concentrations of LPS not only induced severe cellular infiltration, hydrops, and hearing loss, but also a substantial enlargement of the endolymphatic duct and sac. Moreover, LPS injections into perilymph failed to induce hydrops, yet still resulted in cellular infiltration and fibrosis in the cochlea. This suggests that chronic hydrops resulting from an immune challenge of the cochlea may not be due to blockage of the endolymphatic duct and sac, restricting fluid absorption. Furthermore, injecting antigen into endolymph may produce chronic immune-mediated hydrops, and provide a more promising animal model of Meniere's, although animals did not display signs of vestibular dysfunction, and the hearing loss was relatively severe.
为了开发免疫介导的梅尼埃病动物模型，我们将脂多糖（LPS）直接注入豚鼠的中阶，监测了 6 周内的功能和形态变化。根据 LPS 的浓度，变化范围从中度至重度听力损失和内淋巴积水，伴有最小的细胞浸润或纤维化，到充满中阶的密集细胞浸润。有趣的是，较高浓度的 LPS 不仅诱导严重的细胞浸润、积水和听力损失，还导致内淋巴管和囊的显著增大。此外，将 LPS 注入外淋巴未能引起积水，但仍导致耳蜗内的细胞浸润和纤维化。这表明，由于对耳蜗的免疫挑战而导致的慢性积水可能不是由于内淋巴管和囊的阻塞，限制了液体吸收所致。此外，将抗原注入内淋巴可能会产生慢性免疫介导的积水，并提供更有前途的梅尼埃病动物模型，尽管动物没有表现出前庭功能障碍的迹象，且听力损失相对严重。
