Identification of new pharmacological strategies and mechanisms of action for the therapy of Menière´s disease in vivo.

确定体内治疗梅尼埃病的新药理学策略和作用机制。

• 批准号: 220462641
• 负责人: Professor Dr. Martin Canis
• 金额: --
• 依托单位: Klinik und Poliklinik für Hals-, Nasen- und Ohrenheilkunde (Klinikum Großhadern)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2012
• 资助国家: 德国
• 起止时间: 2011-12-31 至 2015-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/220462641?language=en
• 关键词: Identification; new; pharmacological; strategies; mechanisms

Menière´s disease is the second frequent form of peripher vestibular vertigo. As a probable pathophysiological cause an endolymphatic hydrops is discussed. Leading symptoms are recurrent attacks of vertigo, acute hearing loss and tinnitus. Primary treatment goals aim to prevent these attacks and in consequence persisting audiological and vestibular deficits. Prophylactic effects have been described for betahistine a Histamine-H1-receptor-agonist and H3-antagonist. However, betahistine is used only on empirical basis since experimental or even mechanistic data is missing. In the present project we therefore aim to identify new therapeutic strategies for Menière´s disease and mechanisms of action on cellular level. To this end, the regulation of cochlear microcirculation and possibilities of pharmacological interventions are planned to be investigated by 1-photon-intravitalmicroscopy. Furthermore, regulation of terminal vessels is supposed to be analysed on cellular levels by 2-photon-microscopy (intracellular Ca2+ in pericytes and fibrocytes of capillaries, capillary leakage). Functional parameters such as hearing threshold and vestibular evoked myogenic potentials will be further analysed after therapeutic interventions in a chronic hydrops animal model. In regard of the severe symptoms and the large number of patients, new therapeutic options and further insights into the pathophysiological background would be of great clinical and socioeconomic interest.

梅尼埃病是第二种常见的外周前庭眩晕。作为一个可能的病理生理原因的内淋巴积水进行了讨论。主要症状是反复发作的眩晕、急性听力损失和耳鸣。主要治疗目标旨在预防这些发作以及由此导致的持续听力和前庭缺陷。已描述了倍他司汀作为组胺-H1-受体激动剂和H3-拮抗剂的预防作用。然而，倍他司汀仅在经验基础上使用，因为缺少实验数据或甚至机理数据。因此，在本项目中，我们的目标是确定梅尼埃病的新治疗策略和细胞水平的作用机制。为此，耳蜗微循环的调节和药物干预的可能性计划通过1-光子活体显微镜进行研究。此外，终末血管的调节应该通过双光子显微镜在细胞水平上进行分析（毛细血管周细胞和纤维细胞中的细胞内Ca 2+，毛细血管渗漏）。在慢性水肿动物模型中进行治疗干预后，将进一步分析功能参数，如听阈和前庭诱发肌源性电位。鉴于严重的症状和大量的患者，新的治疗选择和进一步了解病理生理学背景将具有重大的临床和社会经济意义。