GABA(A) alpha-1 subunit mediated desynchronization of elevated low frequency oscillations alleviates specific dysfunction in stroke - A case report
GABA(A) alpha-1 subunit mediated desynchronization of elevated low frequency oscillations alleviates specific dysfunction in stroke - A case report
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DOI：
10.1016/j.clinph.2009.11.084
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发表时间：
2010-04-01
影响因子：
4.7
通讯作者：
Stanford, Ian M.
中科院分区：
文献类型：
--
作者：
Hall, Stephen D.;Yamawaki, Naoki;Stanford, Ian M.
目的：广泛报道的催眠药咪唑并吡啶唑吡坦在持续植物人状态下产生的矛盾效应最近在脑损伤和认知障碍患者中得到了复制。然而，这些益处背后的神经机制尚未得到证实。我们采用当代神经影像学方法来研究中风患者 JP 服用唑吡坦后观察到的感觉运动和认知改善情况。方法：我们使用磁共振成像 (MRI) 和磁共振波谱 (MRS) 来解剖和化学表征中风损伤。使用单光子发射计算机断层扫描 (SPECT) 和脑磁图 (MEG) 来识别亚镇静剂量的唑吡坦、佐匹克隆和安慰剂引起的脑血管灌注和神经元网络活动的变化。使用 WAIS-III 和听觉语言任务来测量认知改善情况。结果：MRI 和 MRS 显示左侧颞顶叶区域存在神经元活力完全丧失的病变；同时 SPECT 表明唑吡坦后受影响半球的灌注有所改善。 MEG 表现出梗死周围区域内的高振幅 θ（4-10 Hz）和 β（15-30 Hz）振荡，其功率降低与唑吡坦的摄取以及认知和运动功能的改善一致。结论：在 JP 中，服用低剂量唑吡坦后，功能缺陷和病理振荡似乎同时减少。意义：GABA(A) α-1 敏感的病理振荡去同步可能代表脑损伤的生物标志物和潜在治疗靶点。 (C) 2009 年国际临床神经生理学联合会。由爱思唯尔爱尔兰有限公司出版。保留所有权利。
Objective: The paradoxical effects of the hypnotic imidazopyridine zolpidem, widely reported in persistent vegetative state, have been replicated recently in brain-injured and cognitively impaired patients. However, the neuronal mechanisms underlying these benefits are yet to be demonstrated. We implemented contemporary neuroimaging methods to investigate sensorimotor and cognitive improvements, observed in stroke patient JP following zolpidem administration.Methods: We used Magnetic-Resonance-Imaging (MRI) and Magnetic-Resonance-Spectroscopy (MRS) to anatomically and chemically characterize stroke damage. Single-photon-emission-computed-tomography (SPECT) and magnetoencephalography (MEG) were used to identify changes in cerebrovascular perfusion and neuronal network activity in response to sub-sedative doses of zolpidem, zopiclone and placebo. Cognitive improvements were measured using the WAIS-III and auditory-verbal tasks.Results: MRI and MRS revealed a lesion with complete loss of neuronal viability in the left temporal-parietal region; whilst SPECT indicated improved perfusion in the affected hemisphere following zolpidem. MEG demonstrated high-amplitude theta (4-10 Hz) and beta (15-30 Hz) oscillations within the peri-infarct region, which reduced in power coincident with zolpidem uptake and improvements in cognitive and motor function.Conclusions: In JP, functional deficits and pathological oscillations appear coincidentally reduced following administration of low-dose zolpidem. Significance: GABA(A) alpha-1 sensitive desynchronisation of pathological oscillations may represent a biomarker and potential therapeutic target in brain injury. (C) 2009 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.