Confounding effects of anesthesia on functional activation in rodent brain:: a study of halothane and α-chloralose anesthesia

Confounding effects of anesthesia on functional activation in rodent brain:: a study of halothane and α-chloralose anesthesia
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DOI:
10.1016/j.neuroimage.2004.08.011
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发表时间:
2005-01-01
期刊:
影响因子:
5.7
通讯作者:
Sibson, NR
Sibson, NR
中科院分区:
医学1区
文献类型:
--
作者:
Austin, VC;Blamire, AM;Sibson, NR

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动物模型中的功能磁共振成像 (fMRI) 为比人类更广泛地研究药物作用和潜在生理机制提供了一个平台。然而,通常需要对动物进行麻醉。在这项研究中,我们使用直接皮质刺激的大鼠模型来研究麻醉对啮齿动物功能磁共振成像的影响。具体来说,我们试图回答两个问题(i)基线神经元活动与氟烷麻醉下对刺激的 BOLD 反应之间的关系是什么? (ii) 从氟烷转移到常用麻醉剂 α-氯醛糖后,BOLD 反应有何变化?在第一组实验中,我们发现不同氟烷剂量下的 BOLD 反应幅度没有显着差异,尽管脑电图 (EEG) 记录表明基线神经元活动随着氟烷水平的增加呈剂量依赖性减少。在第二组实验中,从氟烷转移到α-氯醛糖麻醉后,BOLD 反应的空间范围立即明显减小,尽管峰值信号变化没有明显变化。然而,在转移到α-氯醛糖后几个小时,观察到 BOLD 反应的空间范围和峰值高度显着增加,并且对次级皮质和皮质下激活的敏感性增加。这些发现表明,虽然相对于氟烷,α-氯醛糖麻醉与固定刺激的 BOLD 反应更大,但随着时间的推移,反应的程度和幅度存在很大差异,这可能会在使用这种麻醉剂的研究中引入相当大的变异性。 (C) 2004 Elsevier Inc. 保留所有权利。
Functional magnetic resonance imaging (fMRI) in animal models provides a platform for more extensive investigation of drug effects and underlying physiological mechanisms than is possible in humans. However, it is usually necessary for the animal to be anesthetized. In this study, we have used a rat model of direct cortical stimulation to investigate the effects of anesthesia in rodent fMRI. Specifically, we have sought to answer two questions (i) what is the relationship between baseline neuronal activity and the BOLD response to stimulation under halothane anesthesia? And (ii) how does the BOLD response change after transferring from halothane to the commonly used anesthetic alpha-chloralose? In the first set of experiments, we found no significant differences in the amplitude of the BOLD response at the different halothane doses studied, despite electroencephalography (EEG) recordings indicating a dose-dependent reduction in baseline neuronal activity with increasing halothane levels. In the second set of experiments, a reduction in the spatial extent of the BOLD response was apparent immediately after transfer from halothane to alpha-chloralose anesthesia, although no change in the peak signal change was evident. However, several hours after transfer to alpha-chloralose, a significant increase in both the spatial extent and peak height of the BOLD response was observed, as well as an increased sensitivity to secondary cortical and subcortical activation. These findings suggest that, although alpha-chloralose anesthesia is associated with a greater BOLD response for a fixed stimulus relative to halothane, there is substantial variation in the extent and magnitude of the response over time that could introduce considerable variability in studies using this anesthetic. (C) 2004 Elsevier Inc. All rights reserved.