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

meni<e:1>病是外周前庭性眩晕的第二常见形式。作为一个可能的病理生理原因，内淋巴水肿的讨论。主要症状是反复发作的眩晕、急性听力丧失和耳鸣。主要的治疗目标是防止这些攻击和结果持续听力学和前庭功能缺陷。预防作用已被描述为倍他司汀组胺- h1受体激动剂和h3拮抗剂。然而，由于缺乏实验甚至机理数据，倍他司汀仅在经验基础上使用。因此，在目前的项目中，我们的目标是确定meni<e:1>病的新治疗策略和细胞水平上的作用机制。为此，计划通过1光子活体显微镜研究耳蜗微循环的调节和药物干预的可能性。此外，终端血管的调节应该通过2光子显微镜在细胞水平上分析（细胞内Ca2+在周细胞和毛细血管纤维细胞，毛细血管渗漏）。慢性水肿动物模型的功能参数如听阈和前庭诱发肌电位将在治疗干预后进一步分析。考虑到严重的症状和大量的患者，新的治疗方案和对病理生理背景的进一步了解将具有重大的临床和社会经济意义。

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.