Fluid transport in the brain

Physiological Reviews, Journal Year: 2021, Volume and Issue: 102(2), P. 1025 - 1151

Published: May 5, 2021

The brain harbors a unique ability to, figuratively speaking, shift its gears. During wakefulness, the is geared fully toward processing information and behaving, while homeostatic functions predominate during sleep. blood-brain barrier establishes stable environment that optimal for neuronal function, yet imposes physiological problem; transcapillary filtration forms extracellular fluid in other organs reduced to minimum brain. Consequently, depends on special [the cerebrospinal (CSF)] flushed into along perivascular spaces created by astrocytic vascular endfeet. We describe this pathway, coined term glymphatic system, based dependency endfeet their adluminal expression of aquaporin-4 water channels facing CSF-filled spaces. Glymphatic clearance potentially harmful metabolic or protein waste products, such as amyloid-β, primarily active sleep, when drivers, cardiac cycle, respiration, slow vasomotion, together efficiently propel CSF inflow periarterial brain's space contains an abundance proteoglycans hyaluronan, which provide low-resistance hydraulic conduit rapidly can expand shrink sleep-wake cycle. system brain, meets requisites maintain homeostasis similar peripheral organs, considering blood-brain-barrier paths formation egress CSF.

Language: Английский

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Motor and non-motor circuit disturbances in early Parkinson disease: which happens first?

Nature reviews. Neuroscience, Journal Year: 2021, Volume and Issue: 23(2), P. 115 - 128

Published: Dec. 14, 2021

Language: Английский

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Non-invasive MR imaging of human brain lymphatic networks with connections to cervical lymph nodes

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Jan. 11, 2022

Meningeal lymphatic vessels have been described in animal studies, but limited comparable data is available human studies. Here we show dural structures along the venous sinuses dorsal regions and cranial nerves ventral brain. 3D T2-Fluid Attenuated Inversion Recovery magnetic resonance imaging relies on internal signals of protein rich fluid rather than contrast media used present study to visualize major structures. Moreover detect direct connections between channels vascular cervical lymph nodes. We also identify age-related node atrophy thickening lymphatics both regions, findings which reflect reduced output aged

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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Neuroimaging evidence of glymphatic system dysfunction in possible REM sleep behavior disorder and Parkinson’s disease

npj Parkinson s Disease, Journal Year: 2022, Volume and Issue: 8(1)

Published: April 29, 2022

Alpha-synucleinopathy is postulated to be central both idiopathic rapid eye movement sleep behaviour disorder (iRBD) and Parkinson's disease (PD). Growing evidence suggests an association between the diminished clearance of α-synuclein glymphatic system dysfunction. However, accumulating primarily based on clinical data support dysfunction in patients with iRBD PD currently insufficient. This study aimed use diffusion tensor image analysis along perivascular space (DTI-ALPS) evaluate activity its relationship scores severity possible (piRBDs) those PD. Further, we validated correlation ALPS index prognosis longitudinally. Overall, 168 PD, 119 piRBDs, 129 healthy controls were enroled. Among them, 50 had been longitudinally reexamined. Patients exhibited a lower than piRBDs (P = 0.036), patient groups showed < 0.001 P 0.001). The elevated negatively correlated piRBD subgroups. Moreover, was cognitive decline longitudinal analyses. In conclusion, DTI-ALPS provided neuroimaging PD; however, potential assessing pathological progress α-synucleinopathies as indicator worth verifying. Further development imaging methods for function also warranted.

Language: Английский

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Conserved meningeal lymphatic drainage circuits in mice and humans

The Journal of Experimental Medicine, Journal Year: 2022, Volume and Issue: 219(8)

Published: July 1, 2022

Meningeal lymphatic vessels (MLVs) were identified in the dorsal and caudobasal regions of dura mater, where they ensure waste product elimination immune surveillance brain tissues. Whether MLVs exist anterior part murine human skull how connect with glymphatic system extracranial lymphatics remained unclear. Here, we used light-sheet fluorescence microscopy (LSFM) imaging mouse whole-head preparations after OVA-A555 tracer injection into cerebrospinal fluid (CSF) performed real-time vessel-wall (VW) magnetic resonance (VW-MRI) systemic gadobutrol patients neurological pathologies. We observed a conserved three-dimensional anatomy mice humans that aligned dural venous sinuses but not nasal CSF outflow, discovered an extended MLV network around cavernous sinus, exit routes through foramina emissary veins. VW-MRI may provide diagnostic tool for drainage defects diseases.

Language: Английский

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Diffusion along perivascular spaces as marker for impairment of glymphatic system in Parkinson’s disease

npj Parkinson s Disease, Journal Year: 2022, Volume and Issue: 8(1)

Published: Dec. 21, 2022

The brain glymphatic system is involved in the clearance of misfolding α-synuclein, impaired may contribute to progression Parkinson's disease (PD). We aimed analyze diffusion tensor image along perivascular space (DTI-ALPS) and (PVS) burden reveal relationship between PD. A cross-sectional study using a 7 T MRI 76 PD patients 48 controls was performed evaluate brain's system. DTI-ALPS PVS basal ganglia were calculated. Correlation analyses conducted DTI-ALPS, clinical features. detected lower subgroup relative controls, differences more pronounced with Hoehn & Yahr stage greater than two. decreased only evident left hemisphere early but both hemispheres advanced patients. Decreased also correlated longer duration, higher Unified Disease Rating Scale motor score (UPDRS III) UPDRS total scores, as well levodopa equivalent daily dose. Moreover, increased burden, indexes severity. This demonstrated PD, which might initiate from progressively involve right progression. index indicating that metrics could provide supporting evidence an evaluation are potential imaging biomarkers for

Language: Английский

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The Role of Glymphatic System in Alzheimer’s and Parkinson’s Disease Pathogenesis

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

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Matrix metalloproteinase-9 inhibition prevents aquaporin-4 depolarization-mediated glymphatic dysfunction in Parkinson’s disease

Journal of Advanced Research, Journal Year: 2023, Volume and Issue: 56, P. 125 - 136

Published: March 20, 2023

The glymphatic system offers a perivascular pathway for the clearance of pathological proteins and metabolites to optimize neurological functions. Glymphatic dysfunction plays pathogenic role in Parkinson's disease (PD); however, molecular mechanism PD remains elusive. To explore whether matrix metalloproteinase-9 (MMP-9)-mediated β-dystroglycan (β-DG) cleavage is involved regulation aquaporin-4 (AQP4) polarity-mediated PD. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced A53T mice were used this study. function was evaluated using ex vivo imaging. TGN-020, an AQP4 antagonist, administered investigate GM6001, MMP-9 MMP-9/β-DG regulating AQP4. expression distribution AQP4, MMP-9, β-DG assessed western blotting, immunofluorescence, co-immunoprecipitation. ultrastructure basement membrane (BM)-astrocyte endfeet detected transmission electron microscopy. Rotarod open-field tests performed evaluate motor behavior. Perivascular influx efflux cerebral spinal fluid tracers reduced MPTP-induced with impaired polarization. inhibition aggravated reactive astrogliosis, drainage restriction, dopaminergic neuronal loss mice. cleaved upregulated both mice, polarized localization astrocyte endfeet. restored BM-astrocyte endfeet-AQP4 integrity attenuated metabolic perturbations loss. depolarization contributes aggravates pathologies, MMP-9-mediated regulates through polarization PD, which may provide novel insights into pathogenesis

Language: Английский

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Neuroimaging uncovers distinct relationships of glymphatic dysfunction and motor symptoms in Parkinson’s disease

Journal of Neurology, Journal Year: 2023, Volume and Issue: 270(5), P. 2649 - 2658

Published: March 1, 2023

Language: Английский

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