Center for Translational Neuromedicine, Division of Glial Disease and Therapeutics University of Copenhagen, 2200, Denmark.
Institute for Tissue Engineering and Regenerative Medicine (iTERM), Helmholtz Center Munich, Neuherberg, Germany; Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians University Munich, Munich, Germany.
Prog Neurobiol. 2023 Oct;229:102512. doi: 10.1016/j.pneurobio.2023.102512. Epub 2023 Jul 22.
Earlier studies based on 2-photon imaging have shown that glymphatic cerebrospinal fluid (CSF) transport is regulated by the sleep-wake cycle. To examine this association, we used 3DISCO whole-body tissue clearing to map CSF tracer distribution in awake, sleeping and ketamine-xylazine anesthetized mice. The results of our analysis showed that CSF tracers entered the brain to a significantly larger extent in natural sleep or ketamine-xylazine anesthesia than in wakefulness. Furthermore, awake mice showed preferential transport of CSF tracers in the rostro-caudal direction towards the cervical and spinal cord lymphatic vessels, and hence to venous circulation and excretion by the kidneys. The study extends the current literature by showing that CSF dynamics on the whole-body scale is controlled by the state of brain activity.
先前基于双光子成像的研究表明，脑脊髓液（CSF）的神经胶质淋巴转运受睡眠-觉醒周期调控。为了检验这一关联，我们使用 3DISCO 全身组织通透化技术，在清醒、睡眠和氯胺酮-甲苯噻嗪麻醉的小鼠中绘制 CSF 示踪剂的分布。分析结果表明，CSF 示踪剂在自然睡眠或氯胺酮-甲苯噻嗪麻醉中进入大脑的程度明显大于清醒状态。此外，清醒小鼠的 CSF 示踪剂优先向头尾部转运，向颈和脊髓淋巴管，进而向静脉循环和肾脏排泄。该研究通过显示全身尺度的 CSF 动力学受大脑活动状态的控制，扩展了当前的文献。
