Morphological and functional changes in a new animal model of Meniere's disease
Morphological and functional changes in a new animal model of Meniere's disease
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DOI：
10.1038/labinvest.2013.91
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发表时间：
2013-09-01
影响因子：
5
通讯作者：
Yamasoba, Tatsuya
中科院分区：
文献类型：
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作者：
Egami, Naoya;Kakigi, Akinobu;Yamasoba, Tatsuya
这项研究的目的是阐明梅尼埃病(MD)眩晕发作的潜在机制，同时通过一种新的动物模型深入了解内耳的水稳态。我们对豚鼠的前庭系统进行了组织病理学和功能评估。在第一个实验中，所有动物在左耳内淋巴囊电灼后1或4周维持，并给予生理盐水或去氨加压素(血管加压素2型受体激动剂)。取双耳的颞骨，定量评估内淋巴积水的程度。在第二个实验中，在手术后1周或4周，动物在注射生理盐水或去氨加压素后被评估平衡障碍和眼球震颤。在第一个实验中，与其他组相比，术后存活4周并给予去氨加压素组的耳蜗内淋巴间隙和球囊内淋巴间隙比例显著增加。在第二个实验中，所有接受手术并服用去氨加压素的动物都出现了自发性眼震和平衡障碍，而所有接受手术但没有服用去氨加压素的动物都没有症状。我们的动物模型在耳蜗囊和球囊中诱导了严重的内淋巴积水，并表现出一连串的平衡障碍和自发性眼球震颤。这些发现表明，由于急性V2(血管加压素2型受体)介导的效应，去氨加压素的应用可以加剧内淋巴积水，当与内淋巴囊功能障碍结合时，可以导致暂时性前庭异常，类似于MD患者的眩晕发作。
The purpose of this study was to clarify the underlying mechanism of vertiginous attacks in Meniere's disease (MD) while obtaining insight into water homeostasis in the inner ear using a new animal model. We conducted both histopathological and functional assessment of the vestibular system in the guinea-pig. In the first experiment, all animals were maintained 1 or 4 weeks after electrocauterization of the endolymphatic sac of the left ear and were given either saline or desmopressin (vasopressin type 2 receptor agonist). The temporal bones from both ears were harvested and the extent of endolymphatic hydrops was quantitatively assessed. In the second experiment, either 1 or 4 weeks after surgery, animals were assessed for balance disorders and nystagmus after the administration of saline or desmopressin. In the first experiment, the proportion of endolymphatic space in the cochlea and the saccule was significantly greater in ears that survived for 4 weeks after surgery and were given desmopressin compared with other groups. In the second experiment, all animals that underwent surgery and were given desmopressin showed spontaneous nystagmus and balance disorder, whereas all animals that had surgery but without desmopressin administration were asymptomatic. Our animal model induced severe endolymphatic hydrops in the cochlea and the saccule, and showed episodes of balance disorder along with spontaneous nystagmus. These findings suggest that administration of desmopressin can exacerbate endolymphatic hydrops because of acute V2 (vasopressin type 2 receptor)-mediated effects, and, when combined with endolymphathic sac dysfunction, can cause temporary vestibular abnormalities that are similar to the vertiginous attacks in patients with MD.