N-acetyl-L-leucine accelerates vestibular compensation after unilateral labyrinthectomy by action in the cerebellum and thalamus.
N-acetyl-L-leucine accelerates vestibular compensation after unilateral labyrinthectomy by action in the cerebellum and thalamus.
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DOI：
10.1371/journal.pone.0120891
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Zwergal A
中科院分区：
文献类型：
--
作者：
Günther L;Beck R;Xiong G;Potschka H;Jahn K;Bartenstein P;Brandt T;Dutia M;Dieterich M;Strupp M;la Fougère C;Zwergal A
急性单侧前庭损伤导致前庭张力失衡，伴有眼球震颤、头侧倾和姿势失衡。由于中枢前庭代偿（VC），这些缺陷在几天至几周内逐渐减少。本研究在单侧化学性睾丸切除术（UL）大鼠模型中使用行为测试和系列[18 F]-氟脱氧葡萄糖（[18 F]-FDG）-μPET研究了静脉注射N-乙酰-DL-亮氨酸、N-乙酰-L-亮氨酸和N-乙酰-D-亮氨酸对VC的影响。在UL前和UL后第1、3、7和15天进行前庭行为学检查，包括眼球震颤、头侧倾和姿势不平衡的测量以及全脑[18 F]-FDG-μPET的连续测量。在第7天，与假处理组相比，在N-乙酰基-DL-亮氨酸组（p < 0.03）和N-乙酰基-L-亮氨酸组（p < 0.01）中鉴定出姿势不平衡评分的显著降低，但在N-乙酰基-D-亮氨酸组中没有（在每组中，每只大鼠静脉内施用24 mg的剂量，相当于60 mg/kg体重）。DL-和L-组的姿势补偿过程相对于对照组加快了约6天。N-乙酰-L-亮氨酸对姿势补偿的作用依赖于剂量：与60 mg/kg相比，15 mg/kg和3.75 mg/kg剂量无显著影响。在任何剂量下，N-乙酰-L-亮氨酸均不改变眼球震颤或头侧倾的补偿。通过μPET测量局部脑葡萄糖代谢（rCGM）显示，仅N-乙酰-L-亮氨酸而不是N-乙酰-D-亮氨酸在第3天和第7天引起前庭小脑的rCGM显著增加，后外侧丘脑和丘脑底区的rCGM减少。当比较N-乙酰基-L-亮氨酸对UL组和无前庭损伤的假UL组的rCGM的作用时，发现了类似的模式。总之，N-乙酰基-L-亮氨酸以剂量依赖性和特异性的方式改善UL后姿势症状的补偿，最有可能是通过激活前庭小脑和灭活后外侧丘脑。
An acute unilateral vestibular lesion leads to a vestibular tone imbalance with nystagmus, head roll tilt and postural imbalance. These deficits gradually decrease over days to weeks due to central vestibular compensation (VC). This study investigated the effects of i.v. N-acetyl-DL-leucine, N-acetyl-L-leucine and N-acetyl-D-leucine on VC using behavioural testing and serial [18F]-Fluoro-desoxyglucose ([18F]-FDG)-μPET in a rat model of unilateral chemical labyrinthectomy (UL). Vestibular behavioural testing included measurements of nystagmus, head roll tilt and postural imbalance as well as sequential whole-brain [18F]-FDG-μPET was done before and on days 1,3,7 and 15 after UL. A significant reduction of postural imbalance scores was identified on day 7 in the N-acetyl-DL-leucine (p < 0.03) and the N-acetyl-L-leucine groups (p < 0.01), compared to the sham treatment group, but not in the N-acetyl-D-leucine group (comparison for applied dose of 24 mg i.v. per rat, equivalent to 60 mg/kg body weight, in each group). The course of postural compensation in the DL- and L-group was accelerated by about 6 days relative to controls. The effect of N-acetyl-L-leucine on postural compensation depended on the dose: in contrast to 60 mg/kg, doses of 15 mg/kg and 3.75 mg/kg had no significant effect. N-acetyl-L-leucine did not change the compensation of nystagmus or head roll tilt at any dose. Measurements of the regional cerebral glucose metabolism (rCGM) by means of μPET revealed that only N-acetyl-L-leucine but not N-acetyl-D-leucine caused a significant increase of rCGM in the vestibulocerebellum and a decrease in the posterolateral thalamus and subthalamic region on days 3 and 7. A similar pattern was found when comparing the effect of N-acetyl-L-leucine on rCGM in an UL-group and a sham UL-group without vestibular damage. In conclusion, N-acetyl-L-leucine improves compensation of postural symptoms after UL in a dose-dependent and specific manner, most likely by activating the vestibulocerebellum and deactivating the posterolateral thalamus.
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影响因子：
1.6
作者：
Ferber-Viart, C.;Dubreuil, C.;Vidal, P. P.
通讯作者：
Vidal, P. P.
DOI：
10.2310/7070.2007.0050
发表时间：
2007-12-01
期刊：
JOURNAL OF OTOLARYNGOLOGY
影响因子：
--
作者：
Aleisa, Mohammad;Zeitouni, Anthony G.;Cullen, Kathleen E.
通讯作者：
Cullen, Kathleen E.
DOI：
10.1016/0957-4271(94)00026-x
发表时间：
1995-03-01
期刊：
Journal of vestibular research : equilibrium & orientation
影响因子：
--
作者：
Curthoys, I S;Halmagyi, G M
通讯作者：
Halmagyi, G M
影响因子：
5.3
作者：
Meng, Hui;May, Paul J.;Angelaki, Dora E.
通讯作者：
Angelaki, Dora E.
影响因子：
5.5
作者：
Johnston, AR;Seckl, JR;Dutia, MB
通讯作者：
Dutia, MB