Levine Alexandra T, Li Benson, Barnes Paisley, Lomber Stephen G, Butler Blake E
Department of Physiology & Pharmacology, University of Western Ontario, London, Ontario, N6A 5C1, Canada; Brain and Mind Institute, University of Western Ontario, London, Ontario, N6A 3K7, Canada.
Department of Psychology, University of Western Ontario, London, Ontario, N6A 5C2, Canada.
J Neurosci Methods. 2020 Mar 15;334:108603. doi: 10.1016/j.jneumeth.2020.108603. Epub 2020 Jan 23.
Neuroimaging methods including fMRI provide powerful tools to observe whole-brain functional networks. This is particularly powerful in animal models, allowing these networks to be probed using complementary methods. However, most animals must be anesthetized for neuroimaging, giving rise to complications resulting from anesthetic effects on the animal's physiological and neurological functions. For example, an established protocol for feline neuroimaging involves co-administration of ketamine and isoflurane - the latter of which is known to suppress cortical function.
Here, we compare this established protocol to alfaxalone, a single-agent anesthetic for functional neuroimaging. We first compare the two in a controlled environment to assess relative safety and to measure physiological stability over an extended time window. We then compare patterns of auditory and visually-evoked activity measured at 7 T to assess mean signal strength and between-subjects signal variability.
We show that alfaxalone results in more stable respiratory rates over the 120 min testing period, with evidence of smaller between-measurements variability within this time window, when compared to ketamine plus isoflurane. Moreover, we demonstrate that both agents evoke similar mean BOLD signals across animals, but that alfaxalone elicits more consistent BOLD activity in response to sound stimuli across all ROIs observed.
Alfaxalone is observed to be more physiologically stable, evoking a more consistent BOLD signal across animals than the co-administration of ketamine and isoflurane. Thus, an alfaxalone-based protocol may represent a better approach for neuroimaging in animal models requiring anesthesia.
包括功能磁共振成像（fMRI）在内的神经成像方法为观察全脑功能网络提供了强大工具。这在动物模型中尤为强大，使得这些网络能够使用互补方法进行探测。然而，大多数动物在进行神经成像时必须麻醉，这会因麻醉对动物生理和神经功能的影响而引发并发症。例如，一种既定的猫科动物神经成像方案涉及联合使用氯胺酮和异氟烷——后者已知会抑制皮质功能。
在此，我们将这种既定方案与阿法沙龙（一种用于功能神经成像的单剂麻醉药）进行比较。我们首先在受控环境中对两者进行比较，以评估相对安全性并在延长的时间窗口内测量生理稳定性。然后，我们比较在7T时测量的听觉和视觉诱发活动模式，以评估平均信号强度和个体间信号变异性。
我们发现，与氯胺酮加异氟烷相比，在120分钟的测试期内，阿法沙龙使呼吸频率更稳定，有证据表明在此时间窗口内测量值之间的变异性更小。此外，我们证明两种药物在所有动物中诱发的平均血氧水平依赖（BOLD）信号相似，但阿法沙龙在所有观察到的感兴趣区域（ROI）对声音刺激的反应中引发的BOLD活动更一致。
观察到阿法沙龙在生理上更稳定，与氯胺酮和异氟烷联合使用相比，在所有动物中引发的BOLD信号更一致。因此，基于阿法沙龙的方案可能是需要麻醉的动物模型神经成像的更好方法。
