The glymphatic pathway in neurological disorders

The Lancet Neurology, Journal Year: 2018, Volume and Issue: 17(11), P. 1016 - 1024

Published: Oct. 16, 2018

Language: Английский

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Perivascular spaces, glymphatic dysfunction, and small vessel disease

Clinical Science, Journal Year: 2017, Volume and Issue: 131(17), P. 2257 - 2274

Published: Aug. 10, 2017

Cerebral small vessel diseases (SVDs) range broadly in etiology but share remarkably overlapping pathology. Features of SVD including enlarged perivascular spaces (EPVS) and formation abluminal protein deposits cannot be completely explained by the putative pathophysiology. The recently discovered glymphatic system provides a new perspective to potentially address these gaps. This work comprehensive review known factors that regulate function disease mechanisms underlying impairment emphasizing role aquaporin-4 (AQP4)-lined (PVSs), cerebrovascular pulsatility, metabolite clearance play normal CNS physiology. also discusses implications may have on inception progression with aim exploring novel therapeutic targets highlighting key questions remain answered.

Language: Английский

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Understanding the role of the perivascular space in cerebral small vessel disease

Cardiovascular Research, Journal Year: 2018, Volume and Issue: 114(11), P. 1462 - 1473

Published: May 2, 2018

Small vessel diseases (SVDs) are a group of disorders that result from pathological alteration the small blood vessels in brain, including arteries, capillaries and veins. Of 35–36 million people estimated to suffer dementia worldwide, up 65% have an SVD component. Furthermore, causes 20–25% strokes, worsens outcome after stroke is leading cause disability, cognitive impairment poor mobility. Yet underlying cause(s) not fully understood. Magnetic resonance imaging has confirmed enlarged perivascular spaces (PVS) as hallmark feature SVD. In healthy tissue, these proposed form part complex brain fluid drainage system which supports interstitial exchange may also facilitate clearance waste products brain. The pathophysiological signature PVS what this infers about their function interaction with cerebral microcirculation, plus subsequent downstream effects on lesion development been established. Here we discuss potential be unique biomarker for related vascular We propose widening suggests presence peri-vascular cell debris other vicious cycle involving impaired cerebrovascular reactivity, blood-brain barrier dysfunction, inflammation ultimately proteins space, accumulation toxins, hypoxia, tissue damage. Here, outline current knowledge, questions hypotheses regarding understanding dynamics underpinning through common denominator

Language: Английский

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Glymphatic clearance function in patients with cerebral small vessel disease

NeuroImage, Journal Year: 2021, Volume and Issue: 238, P. 118257 - 118257

Published: June 10, 2021

Few studies have focused on the connection between glymphatic dysfunction and cerebral small vessel disease (CSVD), partially due to lack of non-invasive methods measure function. We established modified index for diffusion tensor image analysis along perivascular space (mALPS-index), which was calculated (DTI), compared it with classical detection clearance function Glymphatic MRI after intrathecal administration gadolinium (study 1), analyzed relationship CSVD imaging markers mALPS-index in patients from CIRCLE study (ClinicalTrials.gov ID: NCT03542734) 2). Among 39 included 1, were significantly related ( r = -0.772~-0.844, p < 0.001). A total 330 2. Severer periventricular deep white matter hyperintensities (β -0.332, 0.001; β -0.293, 0.001), number lacunas -0.215, microbleeds -0.152, 0.005), severer enlarged spaces basal ganglia -0.223, 0.001) mALPS-index. Our results indicated that might represent function, could be applied clinic future. play a role development CSVD.

Language: Английский

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Current understanding of neuroinflammation after traumatic brain injury and cell-based therapeutic opportunities

Chinese Journal of Traumatology, Journal Year: 2018, Volume and Issue: 21(3), P. 137 - 151

Published: April 24, 2018

Traumatic brain injury (TBI) remains a major cause of death and disability worldwide. Increasing evidence indicates that TBI is an important risk factor for neurodegenerative diseases including Alzheimer's disease, Parkinson's chronic traumatic encephalopathy. Despite improved supportive rehabilitative care patients, unfortunately, all late phase clinical trials in have yet to yield safe effective neuroprotective treatment. The disappointing may be attributed variability treatment approaches heterogeneity the population patients as well race against time prevent or reduce inexorable cell death. not just acute event but disease. Among many mechanisms involved secondary after TBI, emerging preclinical studies indicate posttraumatic prolonged progressive neuroinflammation associated with neurodegeneration which treatable long initiating injury. This review provides overview recent understanding cell-based therapies target promote functional recovery TBI.

Language: Английский

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Reproducibility of diffusion tensor image analysis along the perivascular space (DTI-ALPS) for evaluating interstitial fluid diffusivity and glymphatic function: CHanges in Alps index on Multiple conditiON acquIsition eXperiment (CHAMONIX) study

Japanese Journal of Radiology, Journal Year: 2021, Volume and Issue: 40(2), P. 147 - 158

Published: Aug. 14, 2021

The diffusion tensor image analysis along the perivascular space (DTI-ALPS) method was developed to evaluate brain's glymphatic function or interstitial fluid dynamics. This study aimed reproducibility of DTI-ALPS and effect modifications in imaging data evaluation.Seven healthy volunteers were enrolled this study. Image acquisition performed for test-retest using a fixed sequence modified methods which included placement region interest (ROI), plane, head position, averaging, number motion-proving gradients, echo time (TE), different scanner. ALPS-index values evaluated change conditions listed above.This by showed very high (intraclass coefficient = 0.828) value. bilateral ROI higher reproducibility. averaging difference scanner did not influence values. However, modification plane position impaired reproducibility, gradients affected from 12-axis DTI 3-axis diffusion-weighted (DWI) good correlation (r 0.86). Also, shorter TE resulted larger value ALPS-index.ALPS index robust under even when scanners used. ALPS influenced gradient axes, sequence. These factors should be uniformed planning studies. possibility develop DWI-ALPS three axes also suggested.

Language: Английский

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Association of MRI Indices of Glymphatic System With Amyloid Deposition and Cognition in Mild Cognitive Impairment and Alzheimer Disease

Neurology, Journal Year: 2022, Volume and Issue: 99(24)

Published: Sept. 19, 2022

The glymphatic system is a whole-brain perivascular network, which promotes CSF/interstitial fluid exchange. Alterations to this may play pivotal role in amyloid β (Aβ) accumulation. However, its involvement Alzheimer disease (AD) pathogenesis not fully understood. Here, we investigated the changes noninvasive MRI measurements related network patients with mild cognitive impairment (MCI) and AD. Additionally, explored associations of measures neuropsychological score, PET standardized uptake value ratio (SUVR), Aβ deposition.

Language: Английский

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Glymphatic system impairment in multiple sclerosis: relation with brain damage and disability

Brain, Journal Year: 2021, Volume and Issue: 145(8), P. 2785 - 2795

Published: Dec. 13, 2021

Recent evidence has shown the existence of a CNS 'waste clearance' system, defined as glymphatic system. Glymphatic abnormalities have been described in several neurodegenerative conditions, including Alzheimer's and Parkinson's disease. function not thoroughly explored multiple sclerosis, where processes are intermingled with inflammatory processes. We aimed to investigate system sclerosis evaluate its association clinical disability, disease course, demyelination neurodegeneration, quantified using different MRI techniques. In this retrospective study, we enrolled 71 patients (49 relapsing-remitting 22 progressive sclerosis) 32 age- sex-matched healthy control subjects. All subjects underwent neurological assessment high-resolution T1, T2 double inversion recovery sequences, diffusion susceptibility weighted imaging. calculated along perivascular space index, proxy for function, cortical deep grey matter volume, white lesion volume normal-appearing microstructural damage. Multiple showed an overall lower index versus controls (estimated mean difference: -0.09, P = 0.01). Both had -0.06, 0.04 -0.19, 0.001 patients). Progressive 0.03). patients, was associated more severe disability (r -0.45, 0.001) longer duration -0.37, 0.002). Interestingly, detected negative between first 4.13 years course -0.38, 0.04) without any thereafter (up 34 duration). Lower higher -0.36, 0.003) -0.41, 0.30, 0.007) 0.42, atrophy, reduced fractional anisotropy increased diffusivity matter. Our results suggest that is impaired especially stages. Impaired measures both neurodegeneration reflects disability. These findings impairment may be pathological mechanism underpinning sclerosis. The dynamic interplay other substrates deserves further investigation.

Language: Английский

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Glymphatic imaging using MRI

Journal of Magnetic Resonance Imaging, Journal Year: 2019, Volume and Issue: 51(1), P. 11 - 24

Published: Aug. 18, 2019

In recent years, the existence of a mass transport system in brain via cerebrospinal fluid (CSF) or interstitial (ISF) has been suggested by many studies. The glymphatic is hypothesized to be waste clearance CSF through perivascular and spaces brain. Tracer studies have primarily used visualize evaluate brain, evidence for this accumulated. initial study that identified was an vivo tracer mice. study, fluorescent tracers were injected into cisterna magna visualized two‐photon microscopy. MRI also function with gadolinium‐based contrast agents (GBCAs) as tracers. A number GBCA evaluating conducted using either intrathecal intravenous injections. Stable isotopes, such 17 O‐labeled water, may since they can detected MRI. addition studies, several other approaches ISF dynamics within including diffusion imaging. Phase evaluation powerful method visualizing flow space. order movement water tissue, diffusion‐weighted represents another promising technique, utilized techniques system. This review will discuss findings these Level Evidence: 5 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2019. 2020;51:11–24.

Language: Английский

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Altered glymphatic system in idiopathic normal pressure hydrocephalus

Parkinsonism & Related Disorders, Journal Year: 2020, Volume and Issue: 82, P. 56 - 60

Published: Nov. 20, 2020

Language: Английский

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