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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900543/ https://www.ncbi.nlm.nih.gov/pubmed/33633540 http://dx.doi.org/10.3389/fnins.2021.639140 |
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author | Natale, Gianfranco Limanaqi, Fiona Busceti, Carla L. Mastroiacovo, Federica Nicoletti, Ferdinando Puglisi-Allegra, Stefano Fornai, Francesco |
author_facet | Natale, Gianfranco Limanaqi, Fiona Busceti, Carla L. Mastroiacovo, Federica Nicoletti, Ferdinando Puglisi-Allegra, Stefano Fornai, Francesco |
author_sort | Natale, Gianfranco |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-7900543 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-79005432021-02-24 Glymphatic System as a Gateway to Connect Neurodegeneration From Periphery to CNS Natale, Gianfranco Limanaqi, Fiona Busceti, Carla L. Mastroiacovo, Federica Nicoletti, Ferdinando Puglisi-Allegra, Stefano Fornai, Francesco Front Neurosci Neuroscience 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. Frontiers Media S.A. 2021-02-09 /pmc/articles/PMC7900543/ /pubmed/33633540 http://dx.doi.org/10.3389/fnins.2021.639140 Text en Copyright © 2021 Natale, Limanaqi, Busceti, Mastroiacovo, Nicoletti, Puglisi-Allegra and Fornai. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neuroscience Natale, Gianfranco Limanaqi, Fiona Busceti, Carla L. Mastroiacovo, Federica Nicoletti, Ferdinando Puglisi-Allegra, Stefano Fornai, Francesco Glymphatic System as a Gateway to Connect Neurodegeneration From Periphery to CNS |
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 | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900543/ https://www.ncbi.nlm.nih.gov/pubmed/33633540 http://dx.doi.org/10.3389/fnins.2021.639140 |
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