Center for Translational Neuromedicine, University of Copenhagen, Copenhagen, Denmark.
Individualized Drug Therapy Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Nat Rev Drug Discov. 2022 Oct;21(10):763-779. doi: 10.1038/s41573-022-00500-9. Epub 2022 Aug 10.
In the past decade, evidence for a fluid clearance pathway in the central nervous system known as the glymphatic system has grown. According to the glymphatic system concept, cerebrospinal fluid flows directionally through the brain and non-selectively clears the interstitium of metabolic waste. Importantly, the glymphatic system may be modulated by particular drugs such as anaesthetics, as well as by non-pharmacological factors such as sleep, and its dysfunction has been implicated in central nervous system disorders such as Alzheimer disease. Although the glymphatic system is best described in rodents, reports using multiple neuroimaging modalities indicate that a similar transport system exists in the human brain. Here, we overview the evidence for the glymphatic system and its role in disease and discuss opportunities to harness the glymphatic system therapeutically; for example, by improving the effectiveness of intrathecally delivered drugs.
在过去的十年中，人们对中枢神经系统中一种被称为“脑淋巴系统”的液体清除途径的证据越来越多。根据脑淋巴系统的概念，脑脊液有方向地流过大脑，并非选择性地清除间质中的代谢废物。重要的是，脑淋巴系统可能会被特定的药物（如麻醉剂）以及非药物因素（如睡眠）所调节，其功能障碍与中枢神经系统疾病（如阿尔茨海默病）有关。尽管脑淋巴系统在啮齿动物中描述得最好，但使用多种神经影像学模式的报告表明，类似的转运系统存在于人类大脑中。在这里，我们综述了脑淋巴系统的证据及其在疾病中的作用，并讨论了利用脑淋巴系统进行治疗的机会；例如，通过提高鞘内给药药物的有效性。
