The Underlying Role of the Glymphatic System and Meningeal Lymphatic Vessels in Cerebral Small Vessel Disease DOI Creative Commons
Yu Tian,

Mengxi Zhao,

Yiyi Chen

et al.

Biomolecules, Journal Year: 2022, Volume and Issue: 12(6), P. 748 - 748

Published: May 25, 2022

There is a growing prevalence of vascular cognitive impairment (VCI) worldwide, and most research has suggested that cerebral small vessel disease (CSVD) the main contributor to VCI. Several potential physiopathologic mechanisms have been proven be involved in process CSVD, such as blood-brain barrier damage, vessels stiffening, venous collagenosis, blood flow reduction, white matter rarefaction, chronic ischaemia, neuroinflammation, myelin subsequent neurodegeneration. However, there still limited overall understanding sequence relative importance these mechanisms. The glymphatic system (GS) meningeal lymphatic (mLVs) are analogs central nervous (CNS). As such, systems play critical roles regulating cerebrospinal fluid (CSF) interstitial (ISF) transport, waste clearance, and, potentially, neuroinflammation. Accumulating evidence played vital animal models CSVD patients with CSVD. Given complexity it was significant understand underlying interaction between transport Here, we provide novel framework based on new advances four aspects, including risk factors, mechanisms, clinical subtypes, cognition, which aims explain how contribute progression proposes comprehensive insight into therapeutic strategy

Language: Английский

The Glymphatic System in Humans: Investigations With Magnetic Resonance Imaging DOI Creative Commons
Shinji Naganawa, Toshiaki Taoka, Rintaro Ito

et al.

Investigative Radiology, Journal Year: 2023, Volume and Issue: 59(1), P. 1 - 12

Published: March 10, 2023

Abstract The concept of the glymphatic system was proposed more than a decade ago as mechanism for interstitial fluid flow and waste removal in central nervous system. function has been shown to be particularly activated during sleep. Dysfunction implicated several neurodegenerative diseases. Noninvasive vivo imaging is expected useful elucidating pathophysiology these Currently, magnetic resonance most commonly used technique evaluate humans, large number studies have reported. This review provides comprehensive overview investigations human using imaging. can divided into 3 categories, including without gadolinium-based contrast agents (GBCAs), with intrathecal administration GBCAs, intravenous GBCAs. purpose examine not only movement brain parenchyma, but also dynamics perivascular subarachnoid spaces, well parasagittal dura meningeal lymphatics. Recent research even extended include eye inner ear. serves an important update guide future directions.

Language: Английский

Citations

42
Age-related alterations in meningeal immunity drive impaired CNS lymphatic drainage DOI Creative Commons
Justin Rustenhoven, Georgios Pavlou, Steffen E. Storck

et al.

The Journal of Experimental Medicine, Journal Year: 2023, Volume and Issue: 220(7)

Published: April 7, 2023

The meningeal lymphatic network enables the drainage of cerebrospinal fluid (CSF) and facilitates removal central nervous system (CNS) waste. During aging in Alzheimer’s disease, impaired promotes buildup toxic misfolded proteins CNS. Reversing this age-related dysfunction represents a promising strategy to augment CNS waste clearance; however, mechanisms underlying decline remain elusive. Here, we demonstrate that alterations immunity underlie impairment. Single-cell RNA sequencing endothelial cells from aged mice revealed their response IFNγ, which was increased meninges due T cell accumulation. Chronic elevation IFNγ young via AAV-mediated overexpression attenuated CSF drainage—comparable deficits observed mice. Therapeutically, neutralization alleviated impairments function. These data suggest manipulation as viable approach normalize alleviate neurological associated with removal.

Language: Английский

Citations

42
Non-invasive modulation of meningeal lymphatics ameliorates ageing and Alzheimer’s disease-associated pathology and cognition in mice DOI Creative Commons
Miao Wang, Congcong Yan, Xi Li

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Feb. 16, 2024

Abstract Meningeal lymphatic vessels (mLVs) have been shown to be involved in amyloid beta (Aβ) clearance, which is considered as a potential therapeutic target for Alzheimer’s disease (AD). In this study, based on the superficial spatial distribution of mLVs, near-infrared light employed modulate drainage, significantly improving cognition both aged and AD (5xFAD APP/PS1) mice, alleviating AD-associated pathology by reducing Aβ deposition, neuroinflammation neuronal damage. Furthermore, transmission electron microscopy imaging RNA sequencing data indicate amelioration mitochondrial metabolism cellular junction meningeal endothelial cells (mLECs) modulation. These studies collectively suggest that treatment can improve cognitive function strengthening scavenging ability mLVs through restoring mLEC function. conclusion, drainage potentiation promotes pathological remission enhancement aging mouse models, offers strategy neurodegenerative diseases.

Language: Английский

Citations

27
The relationship between inflammation, impaired glymphatic system, and neurodegenerative disorders: A vicious cycle DOI Creative Commons

Yu Cai,

Yin Zhang,

Shuo Leng

et al.

Neurobiology of Disease, Journal Year: 2024, Volume and Issue: 192, P. 106426 - 106426

Published: Feb. 6, 2024

The term "glymphatic" emerged roughly a decade ago, marking pivotal point in neuroscience research. glymphatic system, glial-dependent perivascular network distributed throughout the brain, has since become focal of investigation. There is increasing evidence suggesting that impairment system appears to be common feature neurodegenerative disorders, and this exacerbates as disease progression. Nevertheless, factors contributing dysfunction across most disorders remain unclear. Inflammation, however, suspected play role. Dysfunction can lead significant accumulation protein waste products, which trigger inflammation. interaction between inflammation cyclical potentially synergistic. Yet, current research limited, there lack comprehensive models explaining association. In perspective review, we propose novel model inflammation, impaired function, interconnected vicious cycle. By presenting experimental from existing literature, aim demonstrate that: (1) aggravates dysfunction, (2) exacerbated progression, (3) progression promotes Finally, implication proposed discussed.

Language: Английский

Citations

17
New perspectives on the glymphatic system and the relationship between glymphatic system and neurodegenerative diseases DOI Creative Commons
Yujie Sun,

Qiankun Lv,

Junyi Liu

et al.

Neurobiology of Disease, Journal Year: 2025, Volume and Issue: 205, P. 106791 - 106791

Published: Jan. 6, 2025

Neurodegenerative diseases (ND) are characterized by the accumulation of aggregated proteins. The glymphatic system, through its rapid exchange mechanisms between cerebrospinal fluid (CSF) and interstitial (ISF), facilitates movement metabolic substances within brain, serving functions akin to those peripheral lymphatic system. This emerging waste clearance mechanism offers a novel perspective on removal pathological in ND. article elucidates recent discoveries regarding system updates relevant concepts model. It discusses potential roles ND, including Alzheimer's disease (AD), Parkinson's (PD), multiple atrophy (MSA), proposes as therapeutic target for these conditions.

Language: Английский

Citations

2
Meningeal lymphatics-microglia axis regulates synaptic physiology DOI Creative Commons
Kyungdeok Kim,

Daviti Abramishvili,

Siling Du

et al.

Cell, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

Citations

2
Diffusion Tensor Imaging Along the Perivascular Space Index in Different Stages of Parkinson’s Disease DOI Creative Commons
Xinxin Ma, Shuhua Li,

Chunmei Li

et al.

Frontiers in Aging Neuroscience, Journal Year: 2021, Volume and Issue: 13

Published: Nov. 15, 2021

Background: The aim of this study was to evaluate the glymphatic system activity in patients with Parkinson’s disease (PD) using diffusion tensor image analysis along perivascular space (DTI-ALPS) methods. Methods: In total, 71 idiopathic PD and 36 age- sex-matched normal controls (NCs) were involved. Patients divided into early ( n = 35) late 36) subgroups, based on Hoehn Yahr (HY) stages. We calculated diffusivity spaces (ALPS), as well projection fibers association separately, acquire ALPS index. Enlarged (EPVS) periventricular white matter hyperintensities also rated. Differences index between group NCs two subgroups compared. addition, a multivariate logistic regression conducted investigate clinical variables. Results: revealed lower than p 0.010). exhibited significantly 0.006). However, there no marked differences noticed subgroups. group, positive correlation Mini-Mental State Examination (MMSE) score (β 0.021, 0.029) negative EPVS −0.050, 0.034), after controlling for multiple inversely associated age −0.012, 0.004). Conclusion: Impairment is involved PD. DTI-ALPS could be promising biomarker

Language: Английский

Citations

90
The enigma and implications of brain hemispheric asymmetry in neurodegenerative diseases DOI Creative Commons

Noah Lubben,

Elizabeth Ensink, Gerhard A. Coetzee

et al.

Brain Communications, Journal Year: 2021, Volume and Issue: 3(3)

Published: Jan. 1, 2021

The lateralization of the human brain may provide clues into pathogenesis and progression neurodegenerative diseases. Though differing in their presentation underlying pathologies, diseases are all devastating share an intriguing theme asymmetrical pathology clinical symptoms. Parkinson's disease, with its distinctive onset motor symptoms on one side body, stands out this regard, but a review literature reveals asymmetries several other Here, we structure function healthy common genetic epigenetic patterns contributing to development asymmetry health disease. We specifically examine role Alzheimer's amyotrophic lateral sclerosis, multiple interrogate whether these imbalances reveal meaningful about origins also propose hypotheses for how contribute enigmatic features diseases, suggesting choroid plexus, neurochemistry, protein distribution, connectivity vagus nerve. Finally, suggest future studies novel insights through lens asymmetry.

Language: Английский

Citations

78
The Glymphatic System: A Novel Therapeutic Target for Stroke Treatment DOI Creative Commons
Tao� Lv, Bing Zhao,

Qin Hu

et al.

Frontiers in Aging Neuroscience, Journal Year: 2021, Volume and Issue: 13

Published: July 8, 2021

The glymphatic system (GS) is a novel defined brain-wide perivascular transit network between cerebrospinal fluid (CSF) and interstitial solutes that facilitates the clearance of brain metabolic wastes. complicated GS consists periarterial CSF influx pathway, astrocytes-mediated convective transport supported by AQP4 water channels, perivenous efflux pathway. Recent researches indicate dysfunction associated with various neurological disorders, including traumatic injury, hydrocephalus, epilepsy, migraine, Alzheimer’s disease (AD). Meanwhile, also plays pivotal role in pathophysiological process stroke, edema, blood–brain barrier (BBB) disruption, immune cell infiltration, neuroinflammation, neuronal apoptosis. In this review, we illustrated key anatomical structures GS, relationship meningeal lymphatic system, interaction BBB, crosstalk astrocytes other cellular components. addition, contributed to current knowledge about pathology stroke stroke. We further discussed potential use early risk assessment, diagnostics, prognostics, therapeutics

Language: Английский

Citations

67
Cerebral amyloid angiopathy is associated with glymphatic transport reduction and time-delayed solute drainage along the neck arteries DOI
Xinan Chen, Xiaodan Liu, Sunil Koundal

et al.

Nature Aging, Journal Year: 2022, Volume and Issue: 2(3), P. 214 - 223

Published: March 7, 2022

Language: Английский

Citations

59