The Glymphatic System in Central Nervous System Health and Disease: Past, Present, and Future
- PMID: 29195051
- PMCID: PMC5803388
- DOI: 10.1146/annurev-pathol-051217-111018
The Glymphatic System in Central Nervous System Health and Disease: Past, Present, and Future
Abstract
The central nervous system (CNS) is unique in being the only organ system lacking lymphatic vessels to assist in the removal of interstitial metabolic waste products. Recent work has led to the discovery of the glymphatic system, a glial-dependent perivascular network that subserves a pseudolymphatic function in the brain. Within the glymphatic pathway, cerebrospinal fluid (CSF) enters the brain via periarterial spaces, passes into the interstitium via perivascular astrocytic aquaporin-4, and then drives the perivenous drainage of interstitial fluid (ISF) and its solute. Here, we review the role of the glymphatic pathway in CNS physiology, the factors known to regulate glymphatic flow, and the pathologic processes in which a breakdown of glymphatic CSF-ISF exchange has been implicated in disease initiation and progression. Important areas of future research, including manipulation of glymphatic activity aiming to improve waste clearance and therapeutic agent delivery, are also discussed.
Keywords: amyloid-β; aquaporin-4; astrocyte; cerebrospinal fluid; glymphatic; perivascular space.
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References
-
- Trevaskis NL, Kaminskas LM, Porter CJH. From sewer to saviour — targeting the lymphatic system to promote drug exposure and activity. Nat Rev Drug Discov. 2015;14(11):781–803. - PubMed
-
- Oliver G. Lymphatic vasculature development. Nat Rev Immunol. 2004;4(1):35–45. - PubMed
-
- Cserr HF. Physiology of the choroid plexus. Physiol Rev. 1971;51(2):273–311. - PubMed
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