2018 Fiscal Year Final Research Report

Development of drugs that facilitate the processes of vestibular compensation using a new evaluation method with an animal model of vestibular compensation

Research Project

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Project/Area Number	16K11183
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Otorhinolaryngology
Research Institution	The University of Tokushima
Principal Investigator	TAKEDA Noriaki 徳島大学, 大学院医歯薬学研究部(医学域), 教授 (30206982)
Co-Investigator(Kenkyū-buntansha)	坂田ひろみ金沢医科大学, 医学部, 准教授 (50294666) 北村嘉章徳島大学, 大学院医歯薬学研究部(医学域), 講師 (60380028)
Project Period (FY)	2016-04-01 – 2019-03-31
Keywords	前庭代償 / めまい
Outline of Final Research Achievements	We developed a new immunohistochemical method to evaluate the development of vestibular compensation after unilateral labyrinthectomy (UL) in rats. The initial process of vestibular compensation is evaluated using the decline of the frequency of spontaneous nystagmus (SN) as an index in unilaterally labyrinthectomized rats. SN disappeared within 42 hours after UL. The late process of vestibular compensation is evaluated using the decline of the number of MK801-induced Fos-LIR neurons in contralateral medical vestibular nucleus (contra-MVe) as an index in unilaterally labyrinthectomized rats. The number of MK801-induced Fos-LIR neurons in contra-MVe gradually disappeared 14 days after UL. We showed that thioperamide, a histamine H3 receptor antagonist accelerated the late but not initial process of VC after UL. We then showed that diazepam, a GABAA receptor agonist did not accelerate the initial process of VC after UL.
Free Research Field	耳鼻咽喉科学
Academic Significance and Societal Importance of the Research Achievements	メニエール病、めまいを伴う突発性難聴、前庭神経炎などの一側性前庭障害によりめまいや平衡障害が発症するが、前庭代償により次第に軽快する。しかし、前庭代償が不十分のため、長期にめまいや平衡障害を訴える患者は少なくない。本研究結果から、ヒスタミンH3受容体拮抗薬の夜前庭代償を促進できる可能性が示唆された。本研究で用いたthioperamideは臨床では使用できないが、抗めまい薬であるbetahistineがヒスタミンH3受容体拮抗作用を持つことから、前庭代償不全の患者にbetahistineを長期に投与することにより、前庭代償を促進し、難治性めまい患者を治療できる可能性がある。