A fully noninvasive and robust experimental protocol for longitudinal fMRI studies in the rat
A fully noninvasive and robust experimental protocol for longitudinal fMRI studies in the rat
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DOI：
10.1016/j.neuroimage.2005.08.028
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发表时间：
2006-02-15
期刊：
影响因子：
5.7
通讯作者：
Hoehn, M
中科院分区：
文献类型：
--
作者：
Weber, R;Ramos-Cabrer, P;Hoehn, M
功能磁共振成像（fMRI）是研究大脑活动和可塑性变化的独特工具。血氧水平依赖性（BOLD）功能磁共振成像和前爪电刺激的组合已被用作研究大鼠体感通路和大脑康复的标准模型。大多数功能磁共振成像研究都是在用α-氯醛糖麻醉的动物中进行的，因为在这种麻醉下功能代谢耦合得到了最好的保存。然而，由于副作用，α-氯醛糖不适合生存程序，限制其用于同一动物的单一时间点研究。因此，我们开发了一种新的、完全无创的功能磁共振成像方案，使用α(2)-肾上腺素受体激动剂美托咪定镇静并结合经皮血气监测。连续皮下注射美托咪定可导致生理条件长期稳定，所有动物都能很好地耐受重复的功能磁共振成像实验。在所有大鼠连续两次美托咪定疗程中，在对侧初级体感皮层进行前爪刺激时，观察到稳健且可重复的显着 BOLD 信号增加，这与在第三次独立疗程中在 α-氯醛糖作用下在相同动物中观察到的 BOLD 信号增加相似。在美托咪定和α-氯醛糖的作用下，次级体感皮层的激活频率较低。不存在头部运动伪影或非特异性大脑激活。 fMRI 实验后，通过给予拮抗剂阿替美唑可迅速逆转镇静作用。这些结果表明，纵向 fMRI 研究可以在美托咪定镇静下安全地进行，以研究治疗后的功能恢复过程。 (c) 2005 Elsevier Inc. 保留所有权利。
Functional magnetic resonance imaging (fMRI) is a unique tool to study brain activity and plasticity changes. Combination of blood-oxygen level-dependent (BOLD) fMRI and electrical forepaw stimulation has been used as a standard model to study the somatosensory pathway and brain rehabilitation in rats. The majority of fMRI studies have been performed in animals anesthetized with alpha-chloralose as functional-metabolic coupling is best preserved under this anesthesia. However, alpha-chloralose is not suitable for survival procedures due to side effects, limiting its use to single time point studies of the same animal. We therefore developed a new, totally noninvasive fMRI protocol, using sedation with the alpha(2)-adrenoreceptor agonist medetomidine in combination with transcutaneous monitoring of blood gases. The continuous subcutaneous administration of medetomidine resulted in stable physiological conditions over a long time and all animals tolerated the repetitive fMRI experiments well. A robust and reproducible, significant BOLD signal increase was observed upon forepaw stimulation in the contralateral primary somatosensory cortex in two consecutive medetomidine sessions in all rats, which was similar to the BOLD signal increase observed in the same animals under alpha-chloralose during a third independent session. Activation in the secondary somatosensory cortex was observed less frequently under both medetomidine and alpha-chloralose. No head motion artifacts or nonspecific brain activation was present. Sedation was quickly reversed by the administration of the antagonist atipamezole after the fMRI experiment.These results demonstrate that longitudinal fMRI studies can be performed safely under sedation with medetomidine to study functional recovery processes upon therapeutical treatment. (c) 2005 Elsevier Inc. All rights reserved.