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Prog Neurobiol. 2018 Apr - May;163-164:118-143. doi: 10.1016/j.pneurobio.2017.08.007. Epub 2017 Sep 10.

Lymphatic drainage system of the brain: A novel target for intervention of neurological diseases.

Author information

1
Key Laboratory of Cerebral Microcirculation in Universities of Shandong (Taishan Medical University), Department of Neurology, Affiliated Hospital of Taishan Medical University, Tai'an, Shandong 271000, China. Electronic address: blsun88@163.com.
2
Affiliated Hospital of Weifang Medical University, Weifang, Shandong 261031, China.
3
Center of Cerebrovascular Disease Research, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
4
Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, Gangwon 220-701, Republic of Korea.
5
Key Laboratory of Cerebral Microcirculation in Universities of Shandong (Taishan Medical University), Department of Neurology, Affiliated Hospital of Taishan Medical University, Tai'an, Shandong 271000, China.
6
Department of Biological Sciences, Interdisciplinary Graduate Program in Molecular and Cellular Biology, Neuroscience Program, Ohio University, Athens, OH 45701, USA.
7
Key Laboratory of Cerebral Microcirculation in Universities of Shandong (Taishan Medical University), Department of Neurology, Affiliated Hospital of Taishan Medical University, Tai'an, Shandong 271000, China. Electronic address: xyyang@tsmc.edu.cn.

Abstract

The belief that the vertebrate brain functions normally without classical lymphatic drainage vessels has been held for many decades. On the contrary, new findings show that functional lymphatic drainage does exist in the brain. The brain lymphatic drainage system is composed of basement membrane-based perivascular pathway, a brain-wide glymphatic pathway, and cerebrospinal fluid (CSF) drainage routes including sinus-associated meningeal lymphatic vessels and olfactory/cervical lymphatic routes. The brain lymphatic systems function physiological as a route of drainage for interstitial fluid (ISF) from brain parenchyma to nearby lymph nodes. Brain lymphatic drainage helps maintain water and ion balance of the ISF, waste clearance, and reabsorption of macromolecular solutes. A second physiological function includes communication with the immune system modulating immune surveillance and responses of the brain. These physiological functions are influenced by aging, genetic phenotypes, sleep-wake cycle, and body posture. The impairment and dysfunction of the brain lymphatic system has crucial roles in age-related changes of brain function and the pathogenesis of neurovascular, neurodegenerative, and neuroinflammatory diseases, as well as brain injury and tumors. In this review, we summarize the key component elements (regions, cells, and water transporters) of the brain lymphatic system and their regulators as potential therapeutic targets in the treatment of neurologic diseases and their resulting complications. Finally, we highlight the clinical importance of ependymal route-based targeted gene therapy and intranasal drug administration in the brain by taking advantage of the unique role played by brain lymphatic pathways in the regulation of CSF flow and ISF/CSF exchange.

KEYWORDS:

Brain lymphatic drainage; Cerebrospinal fluid; Glymphatic pathway; Interstitial fluid; Meningeal lymphatic vessel; Neurological disease; Olfactory/cervical lymphatic route; Perivascular pathway

PMID:
28903061
DOI:
10.1016/j.pneurobio.2017.08.007
[Indexed for MEDLINE]

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