The Glymphatic System: A Novel Component of Fundamental Neurobiology

Journal of Neuroscience, Journal Year: 2021, Volume and Issue: 41(37), P. 7698 - 7711

Published: Sept. 15, 2021

Throughout the body, lymphatic fluid movement supports critical functions including clearance of excess and metabolic waste. The glymphatic system is analog in CNS. As such, plays a key role regulating directional interstitial movement, waste clearance, and, potentially, brain immunity. enables bulk CSF from subarachnoid space along periarterial spaces, where it mixes with within parenchyma before ultimately exiting via perivenous spaces. This review focuses on important questions about structure this system, why needs transport unexplored aspects transport. We provide evidence that astrocytes blood vessels determine shape perivascular space, controlling fluid. Glymphatic has potential to alter local as well global signaling molecules metabolites. also highlight for cross talk among cardiovascular gastrointestinal tract, system. Much remains be studied, but we propose glymphatic/lymphatic acts cornerstone between body.

Language: Английский

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Emerging roles for dynamic aquaporin-4 subcellular relocalization in CNS water homeostasis

Brain, Journal Year: 2021, Volume and Issue: 145(1), P. 64 - 75

Published: Sept. 8, 2021

Abstract Aquaporin channels facilitate bidirectional water flow in all cells and tissues. AQP4 is highly expressed astrocytes. In the CNS, it enriched astrocyte endfeet, at synapses, glia limitans, where mediates exchange across blood–spinal cord blood–brain barriers (BSCB/BBB), controls cell volume, extracellular space migration. Perivascular enrichment of BSCB/BBB suggests a role glymphatic function. Recently, we have demonstrated that localization also dynamically regulated subcellular level, affecting membrane permeability. Ageing, cerebrovascular disease, traumatic CNS injury, sleep disruption are established emerging risk factors developing neurodegeneration, animal models each, impairment function associated with changes perivascular localization. oedema caused by passive influx through response to osmotic imbalances. We reducing dynamic relocalization reduces accelerates functional recovery rodent models. Given difficulties pore-blocking inhibitors, targeting opens up new treatment avenues for oedema, neurovascular neurodegenerative diseases, provides framework address fundamental questions about homeostasis health disease.

Language: Английский

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The glymphatic system: Current understanding and modeling

iScience, Journal Year: 2022, Volume and Issue: 25(9), P. 104987 - 104987

Published: Aug. 20, 2022

We review theoretical and numerical models of the glymphatic system, which circulates cerebrospinal fluid interstitial around brain, facilitating solute transport. Models enable hypothesis development predictions transport, with clinical applications including drug delivery, stroke, cardiac arrest, neurodegenerative disorders like Alzheimer's disease. sort existing into broad categories by anatomical function: Perivascular flow, transport in brain parenchyma, interfaces to perivascular spaces, efflux routes, links neuronal activity. Needs opportunities for future work are highlighted wherever possible; new models, expanded novel experiments inform could all have tremendous value advancing field.

Language: Английский

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The glymphatic hypothesis: the theory and the evidence

Fluids and Barriers of the CNS, Journal Year: 2022, Volume and Issue: 19(1)

Published: Feb. 3, 2022

Abstract The glymphatic hypothesis proposes a mechanism for extravascular transport into and out of the brain hydrophilic solutes unable to cross blood–brain barrier. It suggests that there is circulation fluid carrying inwards via periarterial routes, through interstitium outwards perivenous routes. This review critically analyses evidence surrounding mechanisms involved in each these stages. There good both influx efflux occur along routes but no principal route outflow perivenous. Furthermore, inflow unlikely be adequate provide would needed account solute efflux. A tenet flow sweeps parenchyma. However, velocity any possible circulatory within too small compared diffusion effective movement. By comparison earlier classical describing proposed entry parenchyma across barrier, movements by diffusion, partly near surfaces carried “preferred routes” including perivascular spaces, white matter tracts subependymal spaces. did not suggest Evidence still incomplete concerning fate leaving brain. large proportion eliminated from go lymph nodes before reaching blood proportions delivered directly or indirectly CSF which then enters are as yet unclear. In addition, understood why how absence AQP4 normally highly expressed on glial endfeet lining reduces rates elimination delivery it remote sites injection. Neither nor adequately explain move into, Features more complete description discussed. All aspects require further study.

Language: Английский

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A mesothelium divides the subarachnoid space into functional compartments

Science, Journal Year: 2023, Volume and Issue: 379(6627), P. 84 - 88

Published: Jan. 5, 2023

The central nervous system is lined by meninges, classically known as dura, arachnoid, and pia mater. We show the existence of a fourth meningeal layer that compartmentalizes subarachnoid space in mouse human brain, designated lymphatic-like membrane (SLYM). SLYM morpho- immunophenotypically similar to mesothelial lining peripheral organs body cavities, it encases blood vessels harbors immune cells. Functionally, close apposition with endothelial venous sinus permits direct exchange small solutes between cerebrospinal fluid blood, thus representing equivalent arachnoid granulations. functional characterization provides fundamental insights into brain barriers transport.

Language: Английский

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Blood-Brain Barrier Overview: Structural and Functional Correlation

Neural Plasticity, Journal Year: 2021, Volume and Issue: 2021, P. 1 - 10

Published: Dec. 6, 2021

The blood-brain barrier (BBB) is a semipermeable and extremely selective system in the central nervous of most vertebrates, that separates blood from brain's extracellular fluid. It plays vital role regulating transport necessary materials for brain function, furthermore, protecting it foreign substances could damage it. In this review, we searched Google Scholar, Pubmed, Web Science, Saudi Digital Library various cells components support development function barrier, as well different pathways to molecules between brain. We also discussed aspects lead BBB dysfunction its neuropathological consequences, with identification some important biomarkers might be used biomarker predict disturbances. This comprehensive overview will pave way future studies focus on developing more specific targeting systems material delivery approach assists combinatorial therapy or nanotherapy destroy modify pathological conditions such tumors stem cell carcinomas.

Language: Английский

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Emerging roles for CNS fibroblasts in health, injury and disease

Nature reviews. Neuroscience, Journal Year: 2021, Volume and Issue: 23(1), P. 23 - 34

Published: Oct. 20, 2021

Language: Английский

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The Glymphatic System (En)during Inflammation

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(14), P. 7491 - 7491

Published: July 13, 2021

The glymphatic system is a fluid-transport that accesses all regions of the brain. It facilitates exchange cerebrospinal fluid and interstitial clears waste from metabolically active Astrocytic endfeet their dense expression aquaporin-4 water channels promote between perivascular spaces neuropil. Cerebrospinal fluids are together transported back to vascular compartment by meningeal cervical lymphatic vessels. Multiple lines work show neurological diseases in general impair transport. Insofar as plays pseudo-lymphatic role central nervous system, it poised play neuroinflammation. In this review, we discuss how association with vessel calls for renewal established concepts on CNS an immune-privileged site. We also potential approaches target combat

Language: Английский

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The glymphatic system: implications for drugs for central nervous system diseases

Nature Reviews Drug Discovery, Journal Year: 2022, Volume and Issue: 21(10), P. 763 - 779

Published: Aug. 10, 2022

Language: Английский

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Neurovascular coupling: motive unknown

Trends in Neurosciences, Journal Year: 2022, Volume and Issue: 45(11), P. 809 - 819

Published: Aug. 19, 2022

Language: Английский

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