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Research progress in glymphatic system of multiple sclerosis
SONG Yuanjun  ZHAO He  GAO Yang 

Cite this article as: SONG Y J, ZHAO H, GAO Y. Research progress in glymphatic system of multiple sclerosis[J]. Chin J Magn Reson Imaging, 2025, 16(3): 133-137. DOI:10.12015/issn.1674-8034.2025.03.022.


[Abstract] Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system with neurological impairment, and its specific pathological mechanism is unknown. Recently, there has been a lot of concern about the role of the glymphatic system (GS) in MS, which may be associated with metabolic waste accumulation and neuroinflammatory responses, and further affect patients' cognitive function. This review reviews the GS-related studies of MS and focuses on its relationship with cognitive impairment, in order to provide new insights into the pathophysiological process, diagnosis, and treatment of MS.
[Keywords] multiple sclerosis；glymphatic system；cognition；magnetic resonance imaging

SONG Yuanjun1   ZHAO He2   GAO Yang2*  

1 Inner Mongolia Medical University, Hohhot 010000, China

2 Department of Imaging Diagnostic, the Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010050, China

Corresponding author: GAO Y, E-mail: 1390903990@qq.com

Conflicts of interest   None.

Received  2025-02-01
Accepted  2025-03-10
DOI: 10.12015/issn.1674-8034.2025.03.022
Cite this article as: SONG Y J, ZHAO H, GAO Y. Research progress in glymphatic system of multiple sclerosis[J]. Chin J Magn Reson Imaging, 2025, 16(3): 133-137. DOI:10.12015/issn.1674-8034.2025.03.022.

[1]
THOMPSON A J, BANWELL B L, BARKHOF F, et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria[J]. Lancet Neurol, 2018, 17(2): 162-173. DOI: . DOI: 10.1016/S1474-4422(17)30470-2.
[2]
TAFTI D, EHSAN M, XIXIS K L. Multiple Sclerosis[M]. In: StatPearls. Treasure Island (FL): StatPearls Publishing; March20, 2024.
[3]
AMIN M, HERSH C M. Updates and advances in multiple sclerosis neurotherapeutics[J]. Neurodegener Dis Manag, 2023, 13(1): 47-70. DOI: DOI:10.2217/nmt-2021-0058.
[4]
ILIFF J J, WANG M, LIAO Y, et al. A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid β[J/OL]. Sci Transl Med, 2012, 4(147): 147ra111-147ra111 [2025-02-01]. https://pubmed.ncbi.nlm.nih.gov/22896675/. DOI: 10.1126/scitranslmed.3003748.
[5]
HABLITZ L M, NEDERGAARD M. The glymphatic system: a novel component of fundamental neurobiology[J]. J Neurosci, 2021, 41(37): 7698-7711. DOI: 10.1523/JNEUROSCI.0619-21.2021.
[6]
CAROTENUTO A, CACCIAGUERRA L, PAGANI E, et al. Glymphatic system impairment in multiple sclerosis: relation with brain damage and disability[J]. Brain, 2022, 145(8): 2785-2795. DOI: 10.1093/brain/awab454.
[7]
IISHIDA K, YAMADA K, NISHIYAMA R, et al. Glymphatic system clears extracellular tau and protects from tau aggregation and neurodegeneration[J/OL]. J Exp Med, 2022, 219(3): e20211275 [2025-02-01]. https://pubmed.ncbi.nlm.nih.gov/35212707/. DOI: 10.1084/jem.20211275.
[8]
PHAM W, LYNCH M, SPITZ G, et al. A critical guide to the automated quantification of perivascular spaces in magnetic resonance imaging[J/OL]. Front Neurosci, 2022, 16: 1021311 [2025-02-01]. https://pubmed.ncbi.nlm.nih.gov/36590285/. DOI: 10.3389/fnins.2022.1021311.
[9]
REHMAN M U, SEHAR N, RASOOL I, et al. Glymphatic pathway: An emerging perspective in the pathophysiology of neurodegenerative diseases[J/OL]. Int J Geriatr Psychiatry, 2024, 39(6): e6104 [2025-02-01]. https://pubmed.ncbi.nlm.nih.gov/38877354/. DOI: 10.1002/gps.6104.
[10]
GAO Y, LIU K, ZHU J. Glymphatic system: an emerging therapeutic approach for neurological disorders[J/OL]. Front Mol Neurosci, 2023, 16: 1138769 [2025-02-01]. https://pubmed.ncbi.nlm.nih.gov/37485040/. DOI: 10.3389/fnmol.2023.1138769.
[11]
BOESPFLUG E L, ILIFF J J. The emerging relationship between interstitial fluid-cerebrospinal fluid exchange, amyloid-β, and sleep[J]. Biol Psychiatry, 2018, 83(4): 328-336. DOI: 10.1016/j.biopsych.2017.11.031.
[12]
ASTARA K, POURNARA C, DE NATALE E R, et al. A novel conceptual framework for the functionality of the glymphatic system[J]. J Neurophysiol, 2023, 129(5): 1228-1236. DOI: 10.1152/jn.00360.2022.
[13]
WANG D J J, HUA J, CAO D, et al. Neurofluids and the glymphatic system: anatomy, physiology, and imaging[J/OL]. Br J Radiol, 2023, 96(1151): 20230016 [2025-02-01]. https://pubmed.ncbi.nlm.nih.gov/37191063/. DOI: 10.1259/bjr.20230016.
[14]
RICHMOND S B, RANE S, HANSON M R, et al. Quantification approaches for magnetic resonance imaging following intravenous gadolinium injection: a window into brain‐wide glymphatic function[J]. Eur J Neurosci, 2023, 57(10): 1689-1704. DOI: 10.1111/ejn.15974.
[15]
TAOKA T, MASUTANI Y, KAWAI H, et al. Evaluation of glymphatic system activity with the diffusion MR technique: diffusion tensor image analysis along the perivascular space (DTI-ALPS) in Alzheimer's disease cases[J]. Jpn J Radiol, 2017, 35: 172-178. DOI: 10.1007/s11604-017-0617-z.
[16]
ZHANG W, ZHOU Y, WANG J, et al. Glymphatic clearance function in patients with cerebral small vessel disease[J/OL]. Neuroimage, 2021, 238: 118257 [2025-02-01]. https://pubmed.ncbi.nlm.nih.gov/34118396/. DOI: 10.1016/j.neuroimage.2021.118257.
[17]
NIU X L, WANG C Y, LIU H Q, et al. Advances in the application of DTI-ALPS in brain glymphoid system related neurological diseases[J]. Chin J Magn Reson Imaging, 2024, 15(5): 192-197. DOI: 10.12015/issn.1674-8034.2024.05.031
[18]
TAOKA T, ITO R, NAKAMICHI R, et al. Diffusion tensor image analysis ALong the perivascular space (DTI-ALPS): revisiting the meaning and significance of the method[J]. Magn Reson Med Sci, 2024, 23(3): 268-290. DOI: 10.2463/mrms.rev.2023-0175.
[19]
XIE Y, ZHU H, YAO Y, et al. Enlarged choroid plexus in relapsing-remitting multiple sclerosis may lead to brain structural changes through the glymphatic impairment[J/OL]. Mult Scler Relat Disord, 2024, 85: 105550 [2025-02-01]. https://pubmed.ncbi.nlm.nih.gov/38493535/. DOI: 10.1016/j.msard.2024.105550.
[20]
KOLBE S C, GARCIA L M, YU N, et al. Lesion volume in relapsing multiple sclerosis is associated with perivascular space enlargement at the level of the basal ganglia[J]. AJNR Am J Neuroradiol, 2022, 43(2): 238-244. DOI: 10.3174/ajnr.A7398.
[21]
ZHANG J, LIU S, WU Y, et al. Enlarged Perivascular Space and Index for Diffusivity Along the Perivascular Space as Emerging Neuroimaging Biomarkers of Neurological Diseases[J/OL]. Cell Mol Neurobiol, 2023, 44(1): 14 [2025-02-01]. https://pubmed.ncbi.nlm.nih.gov/38158515/. DOI: 10.1007/s10571-023-01440-7.
[22]
WONG S M, BACKES W H, DRENTHEN G S, et al. Spectral diffusion analysis of intravoxel incoherent motion MRI in cerebral small vessel disease[J]. J Magn Reson Imaging, 2020, 51(4): 1170-1180. DOI: 10.1002/jmri.26920.
[23]
AKIYAMA Y, YOKOYAMA R, TAKASHIMA H, et al. Accumulation of macromolecules in idiopathic normal pressure hydrocephalus[J]. Neurol Med Chir, 2021, 61(3): 211-218. DOI: 10.2176/nmc.oa.2020-0274.
[24]
WANG Z, SONG Z, ZHOU C, et al. Reduced coupling of global brain function and cerebrospinal fluid dynamics in Parkinson's disease[J]. J Cereb Blood Flow Metab, 2023, 43(8): 1328-1339. DOI: 10.1177/0271678X231164337.
[25]
HAKI M, AL-BIATI H A, AL-TAMEEMI Z S, et al. Review of multiple sclerosis: Epidemiology, etiology, pathophysiology, and treatment[J/OL]. Medicine, 2024, 103(8): e37297 [2025-02-01]. https://pubmed.ncbi.nlm.nih.gov/38394496/. DOI: 10.1097/MD.0000000000037297.
[26]
BAYOUMI A, HASAN K M, THOMAS J A, et al. Glymphatic dysfunction in multiple sclerosis and its association with disease pathology and disability[J]. Mult Scler, 2024, 30(13): 1609-1619. DOI: 10.1177/13524585241280842.
[27]
TOMIZAWA Y, HAGIWARA A, HOSHINO Y, et al. The glymphatic system as a potential biomarker and therapeutic target in secondary progressive multiple sclerosis[J/OL]. Mult Scler Relat Disord, 2024, 83: 105437 [2025-02-01]. https://pubmed.ncbi.nlm.nih.gov/38244527/. DOI: 10.1016/j.msard.2024.105437.
[28]
KIM M, HWANG I, PARK J H, et al. Comparative analysis of glymphatic system alterations in multiple sclerosis and neuromyelitis optica spectrum disorder using MRI indices from diffusion tensor imaging[J/OL]. Human Brain Mapping, 2024, 45(5): e26680 [2025-02-01]. https://pubmed.ncbi.nlm.nih.gov/38590180/. DOI: 10.1002/hbm.26680.
[29]
BORRELLI S, LECLERCQ S, PASI M, et al. Cerebral small vessel disease and glymphatic system dysfunction in multiple sclerosis: A narrative review[J/OL]. Mult Scler Relat Disord, 2024, 91: 105878 [2025-02-01]. https://pubmed.ncbi.nlm.nih.gov/39276600/. DOI: 10.1016/j.msard.2024.105878.
[30]
PREZIOSA P, ROCCA M A, FILIPPI M. Central vein sign and iron rim in multiple sclerosis: ready for clinical use?[J]. Curr Opin Neurol, 2021, 34(4): 505-513. DOI: 10.1097/WCO.0000000000000946.
[31]
RIMKUS C M, OTSUKA F S, NUNES D M, et al. Central vein sign and paramagnetic rim lesions: susceptibility changes in brain tissues and their implications for the study of multiple sclerosis pathology[J/OL]. Diagnostics, 2024, 14(13): 1362 [2025-02-01]. https://pubmed.ncbi.nlm.nih.gov/39001252/. DOI: 10.3390/diagnostics14131362.
[32]
INEICHEN B V, OKAR S V, PROULX S T, et al. Perivascular spaces and their role in neuroinflammation[J]. Neuron, 2022, 110(21): 3566-3581. DOI: 10.1016/j.neuron.2022.10.024.
[33]
INEICHEN B V, CANANAU C, PLATTÉN M, et al. Dilated Virchow-Robin spaces are a marker for arterial disease in multiple sclerosis[J/OL]. EBioMedicine, 2023, 92 [2025-02-01]. https://pubmed.ncbi.nlm.nih.gov/37253317/. DOI: 10.1016/j.ebiom.2023.104631.
[34]
BORRELLI S, GUISSET F, VANDEN BULCKE C, et al. Enlarged perivascular spaces are associated with brain microangiopathy and aging in multiple sclerosis[J]. Mult Scler, 2024, 30(8): 983-993. DOI: 10.1177/13524585241256881.
[35]
LAAKER C, BAENEN C, KOVÁCS K G, et al. Immune cells as messengers from the CNS to the periphery: The role of the meningeal lymphatic system in immune cell migration from the CNS[J/OL]. Front Immunol, 2023, 14: 1233908 [2025-02-01]. https://pubmed.ncbi.nlm.nih.gov/37662908/. DOI: 10.3389/fimmu.2023.1233908.
[36]
MANDOLESI S, NIGLIO T, LENCI C. May Glymphatic Drainage Improve Life Quality in Progressive Multiple Sclerosis Outpatients?[J]. Med Devices, 2024: 417-426. DOI: 10.2147/MDER.S480815.
[37]
SCOLLATO A, LOLLI F, LASTRUCCI G, et al. Case report: A multiple sclerosis patient with imaging features of glymphatic failure benefitted from CSF flow shunting[J/OL]. Front Neurosci, 2022, 16: 863117 [2025-02-01]. https://pubmed.ncbi.nlm.nih.gov/36389221/. DOI: 10.3389/fnins.2022.863117.
[38]
WOJCIK C, FUCHS T A, TRAN H, et al. Staging and stratifying cognitive dysfunction in multiple sclerosis[J]. Mult Scler, 2022, 28(3): 463-471. DOI: 10.1177/13524585211011390.
[39]
HELED E, ALONI R, ACHIRON A. Cognitive functions and disability progression in relapsing-remitting multiple sclerosis: A longitudinal study[J]. Appl Neuropsychol Adult, 2021, 28(2): 210-219. DOI: 10.1080/23279095.2019.1624260.
[40]
FILIPPI M, PREZIOSA P, BARKHOF F, et al. The ageing central nervous system in multiple sclerosis: the imaging perspective[J]. Brain, 2024, 147(11): 3665-3680. DOI: 10.1093/brain/awae251.
[41]
ROCCA M A, MARGONI M, BATTAGLINI M, et al. Emerging perspectives on MRI application in multiple sclerosis: moving from pathophysiology to clinical practice[J/OL]. Radiology, 2023, 307(5): e221512 [2025-02-01]. https://pubmed.ncbi.nlm.nih.gov/37278626/. DOI: 10.1148/radiol.221512.
[42]
JELLINGER K A. Cognitive impairment in multiple sclerosis: from phenomenology to neurobiological mechanisms[J]. J Neural Transm, 2024: 1-29. DOI: 10.1007/s00702-024-02786-y.
[43]
PINTER D, KHALIL M, PIRPAMER L, et al. Long-term course and morphological MRI correlates of cognitive function in multiple sclerosis[J]. Mult Scler, 2021, 27(6): 954-963. DOI: 10.1177/1352458520941474.
[44]
WILCOX O, AMIN M, HANCOCK L, et al. Associations between cognitive impairment and neuroimaging in patients with multiple sclerosis[J]. Arch Clin Neuropsychol, 2024, 39(2): 196-203. DOI: 10.1093/arclin/acad070.
[45]
MARGONI M, PAGANI E, MEANI A, et al. Cognitive impairment is related to glymphatic system dysfunction in pediatric multiple sclerosis[J]. Ann Neurol, 2024, 95(6): 1080-1092. DOI: 10.1002/ana.26911.
[46]
CSOMÓS M, VERÉB D, KOCSIS K, et al. Evaluation of the glymphatic system in relapsing remitting multiple sclerosis by measuring the diffusion along the perivascular space[J/OL]. Magn Reson Imaging, 2025: 110319 [2025-02-01]. https://pubmed.ncbi.nlm.nih.gov/39756667/. DOI: 10.1016/j.mri.2025.110319.
[47]
HAN J, WANG Q J, WANG C H, et al. A study of the correlation between gray matter atrophy in multiple sclerosis and impairment of cognitive function domains[J]. Zhonghua Nei Ke Za Zhi, 2024, 63(7): 666-673. DOI: 10.3760/cma.j.cn112138-20231129-00350.
[48]
HE X, LIU D, ZHANG Q, et al. Voluntary exercise promotes glymphatic clearance of amyloid beta and reduces the activation of astrocytes and microglia in aged mice[J/OL]. Front Mol Neurosci, 2017, 10: 144 [2025-02-01]. https://pubmed.ncbi.nlm.nih.gov/28579942/ DOI: 10.3389/fnmol.2017.00144.
[49]
LIU X, HAO J, YAO E, et al. Polyunsaturated fatty acid supplement alleviates depression-incident cognitive dysfunction by protecting the cerebrovascular and glymphatic systems[J]. Brain Behav Immun, 2020, 89: 357-370. DOI: 10.1016/j.bbi.2020.07.022.
[50]
YAO D, LI R, HAO J, HUANG H, et al. Melatonin alleviates depression-like behaviors and cognitive dysfunction in mice by regulating the circadian rhythm of AQP4 polarization[J/OL]. Transl Psychiatry, 2023, 13(1): 310 [2025-02-01]. https://pubmed.ncbi.nlm.nih.gov/37802998/. DOI: 10.1038/s41398-023-02614-z.

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