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脑膜淋巴管和神经胶质淋巴系统:神经疾病的潜在治疗靶点。

The meningeal lymphatic vessels and the glymphatic system: Potential therapeutic targets in neurological disorders.

机构信息

Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, China.

Department of Neurosurgery, Chengdu Second People's hospital, Chengdu, China.

出版信息

J Cereb Blood Flow Metab. 2022 Aug;42(8):1364-1382. doi: 10.1177/0271678X221098145. Epub 2022 Apr 28.

Abstract

The recent discovery of the meningeal lymphatic vessels (mLVs) and glymphatic pathways has challenged the long-lasting dogma that the central nervous system (CNS) lacks a lymphatic system and therefore does not interact with peripheral immunity. This discovery has reshaped our understanding of mechanisms underlying CNS drainage. Under normal conditions, a close connection between mLVs and the glymphatic system enables metabolic waste removal, immune cell trafficking, and CNS immune surveillance. Dysfunction of the glymphatic-mLV system can lead to toxic protein accumulation in the brain, and it contributes to the development of a series of neurodegenerative disorders, such as Alzheimer's and Parkinson's diseases. The identification of precise cerebral transport routes is based mainly on indirect, invasive imaging of animals, and the results cannot always be applied to humans. Here we review the functions of the glymphatic-mLV system and evidence for its involvement in some CNS diseases. We focus on emerging noninvasive imaging techniques to evaluate the human glymphatic-mLV system and their potential for preclinical diagnosis and prevention of neurodegenerative diseases. Potential strategies that target the glymphatic-mLV system in order to treat and prevent neurological disorders are also discussed.

摘要

脑膜淋巴管 (mLVs) 和神经淋巴通路的最近发现挑战了中枢神经系统 (CNS) 缺乏淋巴系统、因此与外周免疫不相互作用的长期定论。这一发现重塑了我们对 CNS 引流机制的理解。在正常情况下,mLVs 与神经淋巴系统之间的紧密连接可实现代谢废物清除、免疫细胞迁移和 CNS 免疫监视。神经淋巴 -mLV 系统功能障碍可导致脑内毒性蛋白积累,并导致一系列神经退行性疾病的发展,如阿尔茨海默病和帕金森病。精确脑内转运途径的确定主要基于对动物的间接、有创性成像,并且结果并不总是适用于人类。本文综述了神经淋巴 -mLV 系统的功能及其在一些 CNS 疾病中的作用。我们重点介绍新兴的非侵入性成像技术,以评估人类神经淋巴 -mLV 系统及其在神经退行性疾病的临床前诊断和预防中的潜力。还讨论了针对神经淋巴 -mLV 系统的潜在治疗策略,以治疗和预防神经紊乱。

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