Sutton J A, Clauss R P
a ReGen Therapeutics plc and Guildford Clinical Pharmacology Ltd. , Midhurst , West Sussex , UK.
b Department of Nuclear Medicine , Royal Surrey County Hospital , Guildford , Surrey , UK.
Brain Inj. 2017;31(8):1019-1027. doi: 10.1080/02699052.2017.1300836. Epub 2017 May 23.
During 15 years, 23 clinical reports and 6 studies have demonstrated associations between sub-sedative doses of zolpidem and recoveries from brain damage due to strokes, trauma and hypoxia. Clinical findings include unexpected awakenings from vegetative states and regressions of stroke symptoms after dosing that disappear during elimination and reappear on repeat dosing. Initially single-photon emission computed tomography scans showed improved perfusion within, around and distant from infarctions. Then positron emission tomography scans and electroencephalography detected renewed metabolic and neuronal activity. Placebo or a similar, gamma-aminobutyric acid (GABA)-ergic, sedative zopiclone has no such effect. The effect appears only several months after the injury, reflecting recent evidence in mice of substantial differences between the states of GABA receptors in acute and chronic repair phases of recovery. Zolpidem's good safety record and rapid absorption further indicate a need for more clinical trials. List of acronyms: BOLD, Blood-Oxygen-Level Dependent contrast imaging in MRI; CRS, Coma Recovery Scale; CRS-R, Coma Recovery Scale Revised; CSI, Cerebral State Index; CSM, Cerebral State Monitor; DOC, Disorder of Consciousness; EEG, Electro Encephalography; FDG-PET, FluoroDeoxyGlucose-Positron Emission Tomography; FTD, Frontotemporal dementia; GABA, Gamma-Aminobutyric Acid; MCS, Minimally Conscious State; M-EEG, Magneto-Encephalography; MRI, Magnetic Resonance Image; MSN, Median Spiny Neurones; PET, Positron Emission Tomography; PVS, Persistent Vegetative Sate; RLAC, Rancho Los Amigos Cognitive scores; SPECT, Single-photon emission computed tomography; TFES, Tinetti Falls Efficacy Scale; 99mTc HMPAO, Technetium hexamethylpropyleneamine oxime.
在15年的时间里，23份临床报告和6项研究表明，亚镇静剂量的唑吡坦与中风、创伤和缺氧导致的脑损伤恢复之间存在关联。临床发现包括从植物人状态意外苏醒，以及给药后中风症状的消退，这些症状在药物清除期消失，再次给药时又会出现。最初，单光子发射计算机断层扫描显示梗死灶内部、周围及远处的灌注有所改善。随后，正电子发射断层扫描和脑电图检测到代谢和神经元活动重新出现。安慰剂或类似的、γ-氨基丁酸（GABA）能的镇静剂佐匹克隆没有这种效果。这种效果仅在损伤数月后出现，这反映了最近在小鼠身上的证据，即GABA受体在恢复的急性和慢性修复阶段的状态存在显著差异。唑吡坦良好的安全记录和快速吸收进一步表明需要进行更多的临床试验。缩略词列表：BOLD，磁共振成像中的血氧水平依赖对比成像；CRS，昏迷恢复量表；CRS-R，修订版昏迷恢复量表；CSI，脑状态指数；CSM，脑状态监测仪；DOC，意识障碍；EEG，脑电图；FDG-PET，氟脱氧葡萄糖正电子发射断层扫描；FTD，额颞叶痴呆；GABA，γ-氨基丁酸；MCS，微意识状态；M-EEG，脑磁图；MRI，磁共振成像；MSN，中型多棘神经元；PET，正电子发射断层扫描；PVS，持续性植物状态；RLAC，兰乔洛斯阿米戈斯认知评分；SPECT，单光子发射计算机断层扫描；TFES，Tinetti跌倒效能量表；99mTc HMPAO，锝六甲基丙烯胺肟。
