Glymphatic System as a Gateway to Connect Neurodegeneration From Periphery to CNS
The classic concept of the absence of lymphatic vessels in the central nervous system (CNS), suggesting the immune privilege of the brain in spite of its high metabolic rate, was predominant until recent times. On the other hand, this idea left questioned how cerebral interstitial fluid is cleared o...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-02-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnins.2021.639140/full |
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| author | Gianfranco Natale Fiona Limanaqi Carla L. Busceti Federica Mastroiacovo Ferdinando Nicoletti Stefano Puglisi-Allegra Francesco Fornai Francesco Fornai |
| author_facet | Gianfranco Natale Fiona Limanaqi Carla L. Busceti Federica Mastroiacovo Ferdinando Nicoletti Stefano Puglisi-Allegra Francesco Fornai Francesco Fornai |
| author_sort | Gianfranco Natale |
| collection | DOAJ |
| description | The classic concept of the absence of lymphatic vessels in the central nervous system (CNS), suggesting the immune privilege of the brain in spite of its high metabolic rate, was predominant until recent times. On the other hand, this idea left questioned how cerebral interstitial fluid is cleared of waste products. It was generally thought that clearance depends on cerebrospinal fluid (CSF). Not long ago, an anatomically and functionally discrete paravascular space was revised to provide a pathway for the clearance of molecules drained within the interstitial space. According to this model, CSF enters the brain parenchyma along arterial paravascular spaces. Once mixed with interstitial fluid and solutes in a process mediated by aquaporin-4, CSF exits through the extracellular space along venous paravascular spaces, thus being removed from the brain. This process includes the participation of perivascular glial cells due to a sieving effect of their end-feet. Such draining space resembles the peripheral lymphatic system, therefore, the term “glymphatic” (glial-lymphatic) pathway has been coined. Specific studies focused on the potential role of the glymphatic pathway in healthy and pathological conditions, including neurodegenerative diseases. This mainly concerns Alzheimer’s disease (AD), as well as hemorrhagic and ischemic neurovascular disorders; other acute degenerative processes, such as normal pressure hydrocephalus or traumatic brain injury are involved as well. Novel morphological and functional investigations also suggested alternative models to drain molecules through perivascular pathways, which enriched our insight of homeostatic processes within neural microenvironment. Under the light of these considerations, the present article aims to discuss recent findings and concepts on nervous lymphatic drainage and blood–brain barrier (BBB) in an attempt to understand how peripheral pathological conditions may be detrimental to the CNS, paving the way to neurodegeneration. |
| first_indexed | 2024-12-16T16:13:02Z |
| format | Article |
| id | doaj.art-53c62cbe3a214c29a24a9e8afa16db33 |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-12-16T16:13:02Z |
| publishDate | 2021-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj.art-53c62cbe3a214c29a24a9e8afa16db332022-12-21T22:25:09ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2021-02-011510.3389/fnins.2021.639140639140Glymphatic System as a Gateway to Connect Neurodegeneration From Periphery to CNSGianfranco Natale0Fiona Limanaqi1Carla L. Busceti2Federica Mastroiacovo3Ferdinando Nicoletti4Stefano Puglisi-Allegra5Francesco Fornai6Francesco Fornai7Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, ItalyDepartment of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, ItalyIRCCS Neuromed, Pozzilli, ItalyIRCCS Neuromed, Pozzilli, ItalyIRCCS Neuromed, Pozzilli, ItalyIRCCS Neuromed, Pozzilli, ItalyDepartment of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, ItalyIRCCS Neuromed, Pozzilli, ItalyThe classic concept of the absence of lymphatic vessels in the central nervous system (CNS), suggesting the immune privilege of the brain in spite of its high metabolic rate, was predominant until recent times. On the other hand, this idea left questioned how cerebral interstitial fluid is cleared of waste products. It was generally thought that clearance depends on cerebrospinal fluid (CSF). Not long ago, an anatomically and functionally discrete paravascular space was revised to provide a pathway for the clearance of molecules drained within the interstitial space. According to this model, CSF enters the brain parenchyma along arterial paravascular spaces. Once mixed with interstitial fluid and solutes in a process mediated by aquaporin-4, CSF exits through the extracellular space along venous paravascular spaces, thus being removed from the brain. This process includes the participation of perivascular glial cells due to a sieving effect of their end-feet. Such draining space resembles the peripheral lymphatic system, therefore, the term “glymphatic” (glial-lymphatic) pathway has been coined. Specific studies focused on the potential role of the glymphatic pathway in healthy and pathological conditions, including neurodegenerative diseases. This mainly concerns Alzheimer’s disease (AD), as well as hemorrhagic and ischemic neurovascular disorders; other acute degenerative processes, such as normal pressure hydrocephalus or traumatic brain injury are involved as well. Novel morphological and functional investigations also suggested alternative models to drain molecules through perivascular pathways, which enriched our insight of homeostatic processes within neural microenvironment. Under the light of these considerations, the present article aims to discuss recent findings and concepts on nervous lymphatic drainage and blood–brain barrier (BBB) in an attempt to understand how peripheral pathological conditions may be detrimental to the CNS, paving the way to neurodegeneration.https://www.frontiersin.org/articles/10.3389/fnins.2021.639140/fullglymphatic systemlymphatic systemblood–brain barrierneurovascular unitneurodegenerative diseases |
| spellingShingle | Gianfranco Natale Fiona Limanaqi Carla L. Busceti Federica Mastroiacovo Ferdinando Nicoletti Stefano Puglisi-Allegra Francesco Fornai Francesco Fornai Glymphatic System as a Gateway to Connect Neurodegeneration From Periphery to CNS Frontiers in Neuroscience glymphatic system lymphatic system blood–brain barrier neurovascular unit neurodegenerative diseases |
| title | Glymphatic System as a Gateway to Connect Neurodegeneration From Periphery to CNS |
| title_full | Glymphatic System as a Gateway to Connect Neurodegeneration From Periphery to CNS |
| title_fullStr | Glymphatic System as a Gateway to Connect Neurodegeneration From Periphery to CNS |
| title_full_unstemmed | Glymphatic System as a Gateway to Connect Neurodegeneration From Periphery to CNS |
| title_short | Glymphatic System as a Gateway to Connect Neurodegeneration From Periphery to CNS |
| title_sort | glymphatic system as a gateway to connect neurodegeneration from periphery to cns |
| topic | glymphatic system lymphatic system blood–brain barrier neurovascular unit neurodegenerative diseases |
| url | https://www.frontiersin.org/articles/10.3389/fnins.2021.639140/full |
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