Glymphatic-lymphatic coupling: assessment of the evidence from magnetic resonance imaging of humans DOI Creative Commons
Geir Ringstad, Per Kristian Eide

Cellular and Molecular Life Sciences, Journal Year: 2024, Volume and Issue: 81(1)

Published: March 13, 2024

Abstract The discoveries that cerebrospinal fluid participates in metabolic perivascular exchange with the brain and further drains solutes to meningeal lymphatic vessels have sparked a tremendous interest translating these seminal findings from animals humans. A potential two-way coupling between extra-vascular compartment peripheral immune system has implications exceed those concerning neurodegenerative diseases, but also imply central nervous pushed its immunological borders toward periphery, where cross-talk mediated by may play role range of neoplastic diseases. Due non-invasive approach, magnetic resonance imaging typically been preferred methodology attempts image glymphatic lymphatics Even if flourishing, research field is still cradle, interpretations topographically associate reports yet seemed downplay presence previously described anatomical constituents, particularly dura. In this brief review, we illuminate challenges assess evidence for glymphatic-lymphatic coupling. Finally, provide new perspective on how human clearance function possibly be measured future.

Language: Английский

The glymphatic system: Current understanding and modeling DOI Creative Commons
Tomas Bohr, Poul G. Hjorth, Sebastian C. Holst

et al.

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

Citations

171
A Historical Review of Brain Drug Delivery DOI Creative Commons
William M. Pardridge

Pharmaceutics, Journal Year: 2022, Volume and Issue: 14(6), P. 1283 - 1283

Published: June 16, 2022

The history of brain drug delivery is reviewed beginning with the first demonstration, in 1914, that a for syphilis, salvarsan, did not enter brain, due to presence blood–brain barrier (BBB). Owing restricted transport across BBB, FDA-approved drugs CNS have been generally limited lipid-soluble small molecules. Drugs do cross BBB can be re-engineered on endogenous carrier-mediated and receptor-mediated systems, which were identified during 1970s–1980s. By 1990s, multitude technologies emerged, including trans-cranial delivery, CSF disruption, lipid carriers, prodrugs, stem cells, exosomes, nanoparticles, gene therapy, biologics. advantages limitations each these are critically reviewed.

Language: Английский

Citations

132
The glymphatic system: implications for drugs for central nervous system diseases DOI
Terhi J. Lohela, Tuomas O. Lilius, Maiken Nedergaard

et al.

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

Published: Aug. 10, 2022

Language: Английский

Citations

120
Neurovascular coupling: motive unknown DOI
Patrick J. Drew

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

Published: Aug. 19, 2022

Language: Английский

Citations

96
Sleep cycle-dependent vascular dynamics in male mice and the predicted effects on perivascular cerebrospinal fluid flow and solute transport DOI Creative Commons
Laura Bojarskaite, Alexandra Vallet, Daniel M. Bjørnstad

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Feb. 20, 2023

Abstract Perivascular spaces are important highways for fluid and solute transport in the brain enabling efficient waste clearance during sleep. However, underlying mechanisms augmenting perivascular flow sleep unknown. Using two-photon imaging of naturally sleeping male mice we demonstrate cycle-dependent vascular dynamics pial arteries penetrating arterioles: slow, large-amplitude oscillations NREM sleep, a vasodilation REM vasoconstriction upon awakening at end cycle microarousals intermediate These mirrored by changes size slow fluctuations reduction an enlargement after By biomechanical modeling that these likely enhance to levels comparable cardiac pulsation-driven oscillations.

Language: Английский

Citations

79
The Role of Glymphatic System in Alzheimer’s and Parkinson’s Disease Pathogenesis DOI Creative Commons

Francesca R. Buccellato,

Marianna D’Anca, María Serpente

et al.

Biomedicines, Journal Year: 2022, Volume and Issue: 10(9), P. 2261 - 2261

Published: Sept. 13, 2022

Alzheimer's disease (AD) is the most common cause of neurodegenerative dementia, whilst Parkinson's (PD) a movement disorder. These two disorders share accumulation toxic proteins as pathological hallmark. The lack definitive disease-modifying treatments for these neurogenerative diseases has led to hypothesis new pathogenic mechanisms target and design potential therapeutic approaches. recent observation that glymphatic system supposed be responsible cerebrospinal fluid into brain clearance metabolic waste study its involvement in pathogenesis classic proteinopathies. Aquaporin-4 (AQP4), water channel located endfeet astrocyte membrane, considered primary driver system, defective AQP4-mediated drainage been linked objective present review body knowledge links AD PD other lifestyle factors such sleep deprivation exercise may influence function. We will also focus on neuroimaging approaches could identify marker detect changes.

Language: Английский

Citations

72
The choroid plexus links innate immunity to CSF dysregulation in hydrocephalus DOI Creative Commons
Stephanie M. Robert, Benjamin C. Reeves,

Emre Kiziltug

et al.

Cell, Journal Year: 2023, Volume and Issue: 186(4), P. 764 - 785.e21

Published: Feb. 1, 2023

Language: Английский

Citations

71
Neuronal dynamics direct cerebrospinal fluid perfusion and brain clearance DOI
Li-Feng Jiang-Xie, Antoine Drieu, Kesshni Bhasiin

et al.

Nature, Journal Year: 2024, Volume and Issue: 627(8002), P. 157 - 164

Published: Feb. 28, 2024

Language: Английский

Citations

67
Glymphatic imaging: a critical look at the DTI-ALPS index DOI Creative Commons
Geir Ringstad

Neuroradiology, Journal Year: 2024, Volume and Issue: 66(2), P. 157 - 160

Published: Jan. 10, 2024

Language: Английский

Citations

66
Alzheimer’s disease and its treatment–yesterday, today, and tomorrow DOI Creative Commons

A. Y. Kim,

Salman Al Jerdi, Ryan B. MacDonald

et al.

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: May 24, 2024

Alois Alzheimer described the first patient with Alzheimer’s disease (AD) in 1907 and today AD is most frequently diagnosed of dementias. a multi-factorial neurodegenerative disorder familial, life style comorbidity influences impacting global population more than 47 million projected escalation by 2050 to exceed 130 million. In USA demographic encompasses approximately six individuals, expected increase surpass 13 2050, antecedent phase AD, recognized as mild cognitive impairment (MCI), involves nearly 12 individuals. The economic outlay for management AD-related decline estimated at 355 billion USD. addition, intensifying prevalence cases countries modest intermediate income further enhances urgency therapeutically cost-effective treatments improving quality patients their families. This narrative review evaluates pathophysiological basis an initial focus on therapeutic efficacy limitations existing drugs that provide symptomatic relief: acetylcholinesterase inhibitors (AChEI) donepezil, galantamine, rivastigmine, N-methyl-D-aspartate receptor (NMDA) allosteric modulator, memantine. hypothesis amyloid-β (Aβ) tau are appropriate targets have potential halt progress critically analyzed particular clinical trial data anti-Aβ monoclonal antibodies (MABs), namely, aducanumab, lecanemab donanemab. challenges dogma targeting Aβ will benefit majority subjects MABs unlikely be “magic bullet”. A comparison benefits disadvantages different classes forms determining new directions research alternative drug undergoing pre-clinical assessments. we discuss stress importance treatment co-morbidities, including hypertension, diabetes, obesity depression known risk developing AD.

Language: Английский

Citations

21