Fukuda Junya, Matsuda Kazunori, Sato Go, Kitahara Tadashi, Matsuoka Momoyo, Azuma Takahiro, Kitamura Yoshiaki, Tomita Koichi, Takeda Noriaki
Department of Otolaryngology, Graduate School of Biomedical Sciences, University of Tokushima, Tokushima 770-8503, Japan.
Department of Otolaryngology, Tokushima Prefectural Central Hospital, Tokushima 770-8503, Japan.
Brain Sci. 2021 Mar 11;11(3):360. doi: 10.3390/brainsci11030360.
Vestibular compensation (VC) after unilateral labyrinthectomy (UL) consists of the initial and late processes. These processes can be evaluated based on the decline in the frequency of spontaneous nystagmus (SN) and the number of MK801-induced Fos-positive neurons in the contralateral medial vestibular nucleus (contra-MVe) in rats. Histamine H3 receptors (H3R) are reported to be involved in the development of VC.
We examined the effects of betahistine, an H3R antagonist, on the initial and late processes of VC in UL rats.
Betahistine dihydrochloride was continuously administered to the UL rats at doses of 100 and 200 mg/kg/day using an osmotic minipump. MK801 (1.0 mg/kg) was intraperitoneally administered on days 7, 10, 12, and 14 after UL, while Fos-positive neurons were immunohistochemically stained in the contra-MVe.
The SN disappeared after 42 h, and continuous infusion of betahistine did not change the decline in the frequency of SN. The number of MK801-induced Fos-positive neurons in contra-MVe significantly decreased on days 7, 10, and 12 after UL in a dose-dependent manner in the betahistine-treated rats, more so than in the saline-treated rats.
These findings suggest that betahistine facilitated the late, but not the initial, process of VC in UL rats.
单侧迷路切除术后的前庭代偿(VC)包括初始阶段和后期阶段。这些阶段可根据大鼠自发性眼球震颤(SN)频率的下降以及对侧内侧前庭核(对侧MVe)中MK801诱导的Fos阳性神经元的数量来评估。据报道,组胺H3受体(H3R)参与了VC的发展。
我们研究了H3R拮抗剂倍他司汀对单侧迷路切除大鼠VC初始阶段和后期阶段的影响。
使用渗透微型泵以100和200mg/kg/天的剂量持续给单侧迷路切除大鼠注射二盐酸倍他司汀。在单侧迷路切除术后第7、10、12和14天腹腔注射MK801(1.0mg/kg),同时对对侧MVe中的Fos阳性神经元进行免疫组织化学染色。
42小时后SN消失,持续输注倍他司汀并未改变SN频率的下降。在倍他司汀治疗的大鼠中,单侧迷路切除术后第7、10和12天,对侧MVe中MK801诱导的Fos阳性神经元数量以剂量依赖方式显著减少,比生理盐水治疗的大鼠减少得更多。
这些发现表明,倍他司汀促进了单侧迷路切除大鼠VC的后期阶段,但未促进初始阶段。