Impact of Vestibular suppressants on vestibular compensation: animal model studies

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K09911
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56050:Otorhinolaryngology-related
• Research Institution: The University of Tokushima
• Principal Investigator: MATSUDA Kazunori 徳島大学, 大学院医歯薬学研究部(医学域), 徳島大学専門研究員 (60721785)
• Co-Investigator(Kenkyū-buntansha): 武田 憲昭 徳島大学, 大学院医歯薬学研究部(医学域), 教授 (30206982) ; 佐藤 豪 徳島大学, 病院, 講師 (30464358)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 前庭代償 / 免疫組織化学法 / MK801 / Fos / ヒスタミンH3受容体 / GABA作動薬 / 自発眼振 / 前庭神経核

Outline of Final Research Achievements

we used immunohistochemical technique and developed the new evaluation method of vestibular compensation (VC) in unilateral labyrinthectomized rats. VC consists of two processes: the inhibition of the contralateral vestibular nucleus activities in the initial process, and the restoration of the ipsilateral medial vestibular nuclear in the late process after UL. The initial process of VC was evaluated by the decline of spontaneous nystagmus frequency after UL, and the late process of VC considered to be the decline of MK801-induced Fos-like immunoreactive neurons number in the contra-MVe after unilateral labyrinthectomy (UL) in rats.
We then used this evaluation method and showed that thioperamide and betahistine, histamine H3 receptor antagonists, accelerated the late but not initial process of VC.　Further, we performed the nonlinear regression analysis using the decline of SN frequency after UL, showed that diazepam, GABAA receptor agonist, accelerated the initial process of VC.

Free Research Field

めまい平衡障害

Academic Significance and Societal Importance of the Research Achievements

現在、我が国は世界でも類を見ない超高齢社会に突入している。高齢者において前庭代償遅延によるふらつきは転倒・骨折の危険因子となり、健康寿命を短縮させる要因となる。今後、超高齢化社会を迎える日本において、前庭代償に影響を及ぼす薬剤の検討と前庭代償を促進させる薬剤の開発が求められる。本研究は、薬剤における前庭代償に与える影響についての科学的根拠となり、前庭代償の促進に着眼した抗めまい薬の開発にむけた臨床的応用へとつながり、前庭代償を促進する新規薬剤の開発も可能となりうる。このことは、超高齢社会に向けたフレイルや寝たきりの予防戦略の構築に貢献し、超高齢化のすすむ我が国において社会的意義が大きい。