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Research progress in central nervous system diseases and the brain lymphatic system
HE Xi  CHEN Li  WANG Weicheng 

Cite this article as: HE X, CHEN L, WANG W C. Research progress in central nervous system diseases and the brain lymphatic system[J]. Chin J Magn Reson Imaging, 2025, 16(3): 127-132. DOI:10.12015/issn.1674-8034.2025.03.021.


[Abstract] Traditional views held that the central nervous system(CNS) lacks a lymphatic system for metabolic waste clearance. However, recent advances in brain waste clearance research have revealed the existence of specialized lymphatic structures within CNS, namely the glymphatic system and meningeal lymphatic vessels.These discoveries have been validated through both animal models and human studies. This systematically article reviews the anatomical organization and physiological functions of the brain's lymphatic system, examines factors modulating its activity, and evaluates current detection methodologies.Furthermore, we synthesize emerging evidence highlighting the involvement of this system in the pathogenesis of various CNS disorders, with the goal of adwancing neuroimaging strategies and therapeutic interventions for these conditions.
[Keywords] central nervous system diseases；glymphatic system；meningeal lymphatic vessels；magnetic resonance imaging

HE Xi   CHEN Li   WANG Weicheng*  

Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, China

Corresponding author: WANG W C, E-mail: wwc_7973@qq.com

Conflicts of interest   None.

Received  2025-01-27
Accepted  2025-03-10
DOI: 10.12015/issn.1674-8034.2025.03.021
Cite this article as: HE X, CHEN L, WANG W C. Research progress in central nervous system diseases and the brain lymphatic system[J]. Chin J Magn Reson Imaging, 2025, 16(3): 127-132. DOI:10.12015/issn.1674-8034.2025.03.021.

[1]
LIAN X Y, GAO X, LIU X H, et al. Progress in the application of diffusion tensor image analysis along the perivascular space in brain glymphatic system related diseases[J]. Int J Med Radiol, 2024, 47(1): 37-42. DOI: 10.19300/j.2024.Z21094.
[2]
BAH T M, SILER D A, IBRAHIM A H, et al. Fluid dynamics in aging-related dementias[J/OL]. Neurobiol Dis, 2023, 177: 105986 [2025-01-27]. https://pubmed.ncbi.nlm.nih.gov/36603747/. DOI: 10.1016/j.nbd.2022.105986.
[3]
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): 147ra11 [2025-01-27]. https://pubmed.ncbi.nlm.nih.gov/22896675/. DOI: 10.1126/scitranslmed.3003748.
[4]
DING Z, FAN X, ZHANG Y, et al. The glymphatic system: a new perspective on brain diseases[J/OL]. Front Aging Neurosci, 2023, 15: 1179988 [2025-01-27]. https://pubmed.ncbi.nlm.nih.gov/37396658/. DOI: 10.3389/fnagi.2023.1179988.
[5]
LOUVEAU A, SMIRNOV I, KEYES T J, et al. Structural and functional features of central nervous system lymphatic vessels[J]. Nature, 2015, 523(7560): 337-341. DOI: 10.1038/nature14432.
[6]
ASPELUND A, ANTILA S, PROULX S T, et al. A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules[J]. J Exp Med, 2015, 212(7): 991-999. DOI: 10.1084/jem.20142290.
[7]
HLADKY S B, BARRAND M A. The glymphatic hypothesis: the theory and the evidence[J/OL]. Fluids Barriers CNS, 2022, 19(1): 9 [2025-01-27]. https://pubmed.ncbi.nlm.nih.gov/35115036/. DOI: 10.1186/s12987-021-00282-z.
[8]
RASMUSSEN M K, MESTRE H, NEDERGAARD M. Fluid transport in the brain[J]. Physiol Rev, 2022, 102(2): 1025-1151. DOI: 10.1152/physrev.00031.2020.
[9]
YAMADA K, IWATSUBO T. Involvement of the glymphatic/meningeal lymphatic system in Alzheimer's disease: insights into proteostasis and future directions[J/OL]. Cell Mol Life Sci, 2024, 81(1): 192 [2025-01-27]. https://pubmed.ncbi.nlm.nih.gov/38652179/. DOI: 10.1007/s00018-024-05225-z.
[10]
LOPES D M, LLEWELLYN S K, HARRISON I F. Propagation of tau and α-synuclein in the brain: therapeutic potential of the glymphatic system[J/OL]. Transl Neurodegener, 2022, 11(1): 19 [2025-01-27]. https://pubmed.ncbi.nlm.nih.gov/35314000/. DOI: 10.1186/s40035-022-00293-2.
[11]
SALVADOR A F M, ABDULJAWAD N, KIPNIS J. Meningeal Lymphatics in Central Nervous System Diseases[J]. Annu Rev Neurosci, 2024, 47(1): 323-344. DOI: 10.1146/annurev-neuro-113023-103045.
[12]
ISHIDA 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 [2025-01-27]. https://pubmed.ncbi.nlm.nih.gov/35212707/. DOI: 10.1084/jem.20211275.
[13]
LOPES D M, WELLS J A, MA D, et al. Glymphatic inhibition exacerbates tau propagation in an Alzheimer's disease model[J/OL]. Alzheimers Res Ther, 2024, 16(1): 71 [2025-01-27]. https://pubmed.ncbi.nlm.nih.gov/38576025/. DOI: 10.1186/s13195-024-01439-2.
[14]
SIMON M, WANG M X, ISMAIL O, et al. Loss of perivascular aquaporin-4 localization impairs glymphatic exchange and promotes amyloid β plaque formation in mice[J/OL]. Alzheimers Res Ther, 2022, 14(1): 59 [2025-01-27]. DOI: 10.1186/s13195-022-00999-5.
[15]
PENG W, YUAN Y, LEI J, et al. Long-Term High-Fat Diet Impairs AQP4-Mediated Glymphatic Clearance of Amyloid Beta[J]. Mol Neurobiol, 2025, 62(1): 1079-1093. DOI: 10.1007/s12035-024-04320-3.
[16]
SI X, DAI S, FANG Y, et al. Matrix metalloproteinase-9 inhibition prevents aquaporin-4 depolarization-mediated glymphatic dysfunction in Parkinson's disease[J]. J Adv Res, 2024, 56: 125-136. DOI: 10.1016/j.jare.2023.03.004.
[17]
XIE L, KANG H, XU Q, et al. Sleep drives metabolite clearance from the adult brain[J]. Science, 2013, 342(6156): 373-377. DOI: 10.1126/science.1241224.
[18]
SEMYACHKINA-GLUSHKOVSKAYA O, FEDOSOV I, PENZEL T, et al. Brain Waste Removal System and Sleep: Photobiomodulation as an Innovative Strategy for Night Therapy of Brain Diseases[J/OL]. Int J Mol Sci, 2023, 24(4): 3221 [2025-01-27]. https://pubmed.ncbi.nlm.nih.gov/36834631/. DOI: 10.3390/ijms24043221.
[19]
HAUGLUND N L, ANDERSEN M, TOKARSKA K, et al. Norepinephrine-mediated slow vasomotion drives glymphatic clearance during sleep[J/OL]. Cell, 2025, 188(3): 606-622.e17 [2025-01-27]. https://pubmed.ncbi.nlm.nih.gov/39788123/. DOI: 10.1016/j.cell.2024.11.027.
[20]
MEINHOLD L, GENNARI A G, BAUMANN-VOGEL H, et al. T2 MRI visible perivascular spaces in Parkinson's disease: clinical significance and association with polysomnography measured sleep[J/OL]. Sleep, 2025, 48(1): zsae233 [2025-01-27]. https://pubmed.ncbi.nlm.nih.gov/39377177/. DOI: 10.1093/sleep/zsae233.
[21]
SHANG Y, YU L, XING H, et al. Diffusion Tensor Imaging Analysis Along the Perivascular Space (DTI-ALPS) Demonstrates That Sleep Disorders Exacerbate Glymphatic Circulatory Impairment and Cognitive Impairment in Patients with Alzheimer's Disease[J]. Nat Sci Sleep, 2024, 16: 2205-2215. DOI: 10.2147/nss.S496607.
[22]
HAN G, JIAO B, ZHANG Y, et al. Arterial pulsation dependence of perivascular cerebrospinal fluid flow measured by dynamic diffusion tensor imaging in the human brain[J/OL]. Neuroimage, 2024, 297: 120653 [2025-01-27]. https://pubmed.ncbi.nlm.nih.gov/38795798/. DOI: 10.1016/j.neuroimage.2024.120653.
[23]
XIE L, ZHANG Y, HONG H, et al. Higher intracranial arterial pulsatility is associated with presumed imaging markers of the glymphatic system: An explorative study[J/OL]. Neuroimage, 2024, 288: 120524 [2025-01-27]. https://pubmed.ncbi.nlm.nih.gov/38278428/. DOI: 10.1016/j.neuroimage.2024.120524.
[24]
ZHOU Y, XUE R, LI Y, et al. Impaired Meningeal Lymphatics and Glymphatic Pathway in Patients with White Matter Hyperintensity[J/OL]. Adv Sci (Weinh), 2024, 11(26): e2402059 [2025-01-27]. https://pubmed.ncbi.nlm.nih.gov/38704728/. DOI: 10.1002/advs.202402059.
[25]
TAOKA T, JOST G, FRENZEL T, et al. Impact of the Glymphatic System on the Kinetic and Distribution of Gadodiamide in the Rat Brain: Observations by Dynamic MRI and Effect of Circadian Rhythm on Tissue Gadolinium Concentrations[J]. Invest Radiol, 2018, 53(9): 529-534. DOI: 10.1097/rli.0000000000000473.
[26]
ZHANG M, TANG J, XIA D, et al. Evaluation of glymphatic-meningeal lymphatic system with intravenous gadolinium-based contrast-enhancement in cerebral small-vessel disease[J]. Eur Radiol, 2023, 33(9): 6096-6106. DOI: 10.1007/s00330-023-09796-6.
[27]
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(4): 172-178. DOI: 10.1007/s11604-017-0617-z.
[28]
ZHANG W, ZHOU Y, WANG J, et al. Glymphatic clearance function in patients with cerebral small vessel disease[J/OL]. Neuroimage, 2021, 238: 118257 [2025-01-27]. https://pubmed.ncbi.nlm.nih.gov/34118396/. DOI: 10.1016/j.neuroimage.2021.118257.
[29]
HUANG S Y, ZHANG Y R, GUO Y, et al. Glymphatic system dysfunction predicts amyloid deposition, neurodegeneration, and clinical progression in Alzheimer's disease[J]. Alzheimers Dement, 2024, 20(5): 3251-3269. DOI: 10.1002/alz.13789.
[30]
SHEN T, YUE Y, BA F, et al. Diffusion along perivascular spaces as marker for impairment of glymphatic system in Parkinson's disease[J/OL]. NPJ Parkinsons Dis, 2022, 8(1): 174 [2025-01-27]. https://pubmed.ncbi.nlm.nih.gov/36543809/. DOI: 10.1038/s41531-022-00437-1.
[31]
BARISANO G, LYNCH K M, SIBILIA F, et al. Imaging perivascular space structure and function using brain MRI[J/OL]. Neuroimage, 2022, 257: 119329 [2025-01-27]. https://pubmed.ncbi.nlm.nih.gov/35609770/. DOI: 10.1016/j.neuroimage.2022.119329.
[32]
ZHANG X, WANG Y, JIAO B, et al. Glymphatic system impairment in Alzheimer's disease: associations with perivascular space volume and cognitive function[J]. Eur Radiol, 2024, 34(2): 1314-1323. DOI: 10.1007/s00330-023-10122-3.
[33]
CHOI J D, MOON Y, KIM H J, et al. Choroid Plexus Volume and Permeability at Brain MRI within the Alzheimer Disease Clinical Spectrum[J]. Radiology, 2022, 304(3): 635-645. DOI: 10.1148/radiol.212400.
[34]
HONG H, HONG L, LUO X, et al. The relationship between amyloid pathology, cerebral small vessel disease, glymphatic dysfunction, and cognition: a study based on Alzheimer's disease continuum participants[J/OL]. Alzheimers Res Ther, 2024, 16(1): 43 [2025-01-27]. https://pubmed.ncbi.nlm.nih.gov/38378607/. DOI: 10.1186/s13195-024-01407-w.
[35]
EISMA J J, MCKNIGHT C D, HETT K, et al. Deep learning segmentation of the choroid plexus from structural magnetic resonance imaging (MRI): validation and normative ranges across the adult lifespan[J/OL]. Fluids Barriers CNS, 2024, 21(1): 21 [2025-01-27]. https://pubmed.ncbi.nlm.nih.gov/38424598/. DOI: 10.1186/s12987-024-00525-9.
[36]
SIGHENCEA M G, POPESCU R, TRIFU S C. From Fundamentals to Innovation in Alzheimer's Disease: Molecular Findings and Revolutionary Therapies[J/OL]. Int J Mol Sci, 2024, 25(22): 12311 [2025-01-27]. https://pubmed.ncbi.nlm.nih.gov/39596378/. DOI: 10.3390/ijms252212311.
[37]
CHACHAJ A, GĄSIOROWSKI K, SZUBA A, et al. The Lymphatic System In The Brain Clearance Mechanisms - New Therapeutic Perspectives For Alzheimer's Disease[J]. Curr Neuropharmacol, 2023, 21(2): 380-391. DOI: 10.2174/1570159x20666220411091332.
[38]
HSU J L, WEI Y C, TOH C H, et al. Magnetic Resonance Images Implicate That Glymphatic Alterations Mediate Cognitive Dysfunction in Alzheimer Disease[J]. Ann Neurol, 2023, 93(1): 164-174. DOI: 10.1002/ana.26516.
[39]
FORMOLO D A, YU J, LIN K, et al. Leveraging the glymphatic and meningeal lymphatic systems as therapeutic strategies in Alzheimer's disease: an updated overview of nonpharmacological therapies[J/OL]. Mol Neurodegener, 2023, 18(1): 26 [2025-01-27]. https://pubmed.ncbi.nlm.nih.gov/37081555/. DOI: 10.1186/s13024-023-00618-3.
[40]
REN L, YE J. Commentary: The central lymphatic drainage in pharmacological, surgical and physical therapies of Alzheimer's disease[J]. Acta Pharm Sin B, 2024, 14(7): 3291-3293. DOI: 10.1016/j.apsb.2024.04.018.
[41]
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.
[42]
YUE Y, ZHANG X, LV W, et al. Interplay between the glymphatic system and neurotoxic proteins in Parkinson's disease and related disorders: current knowledge and future directions[J]. Neural Regen Res, 2024, 19(9): 1973-1980. DOI: 10.4103/1673-5374.390970.
[43]
REN J, XIE D, WANG L, et al. Glymphatic system dysfunction as a biomarker of disease progression in Parkinson's disease: neuroimaging evidence from longitudinal cohort studies[J/OL]. J Neurol, 2025, 272(3): 196 [2025-01-27]. https://pubmed.ncbi.nlm.nih.gov/39932513/. DOI: 10.1007/s00415-025-12944-1.
[44]
PANG H, WANG J, YU Z, et al. Glymphatic function from diffusion-tensor MRI to predict conversion from mild cognitive impairment to dementia in Parkinson's disease[J]. J Neurol, 2024, 271(8): 5598-5609. DOI: 10.1007/s00415-024-12525-8.
[45]
DUERING M, BIESSELS G J, BRODTMANN A, et al. Neuroimaging standards for research into small vessel disease-advances since 2013[J]. Lancet Neurol, 2023, 22(7): 602-618. DOI: 10.1016/s1474-4422(23)00131-x.
[46]
ANG P S, ZHANG D M, AZIZI S A, et al. The glymphatic system and cerebral small vessel disease[J/OL]. J Stroke Cerebrovasc Dis, 2024, 33(3): 107557 [2025-01-27]. https://pubmed.ncbi.nlm.nih.gov/38198946/. DOI: 10.1016/j.jstrokecerebrovasdis.2024.107557.
[47]
TIAN Y, CAI X, ZHOU Y, et al. Impaired glymphatic system as evidenced by low diffusivity along perivascular spaces is associated with cerebral small vessel disease: a population-based study[J]. Stroke Vasc Neurol, 2023, 8(5): 413-423. DOI: 10.1136/svn-2022-002191.
[48]
DENG X, DING J, LIU C, et al. Progressive histological and behavioral deterioration of a novel mouse model of secondary hydrocephalus after subarachnoid hemorrhage[J/OL]. Sci Rep, 2024, 14(1): 31794 [2025-01-27]. https://pubmed.ncbi.nlm.nih.gov/39738570/. DOI: 10.1038/s41598-024-82843-4.
[49]
WANG J, LV T, JIA F, et al. Subarachnoid hemorrhage distinctively disrupts the glymphatic and meningeal lymphatic systems in beagles[J]. Theranostics, 2024, 14(15): 6053-6070. DOI: 10.7150/thno.100982.
[50]
EIDE P K, UNDSETH R M, PRIPP A, et al. Impact of Subarachnoid Hemorrhage on Human Glymphatic Function: A Time-Evolution Magnetic Resonance Imaging Study[J]. Stroke, 2025, 56(3): 678-691. DOI: 10.1161/strokeaha.124.047739.
[51]
WANG Y J, SUN Y R, PEI Y H, et al. The lymphatic drainage systems in the brain: a novel target for ischemic stroke?[J]. Neural Regen Res, 2023, 18(3): 485-491. DOI: 10.4103/1673-5374.346484.
[52]
ZHU J, MO J, LIU K, et al. Glymphatic System Impairment Contributes to the Formation of Brain Edema After Ischemic Stroke[J]. Stroke, 2024, 55(5): 1393-1404. DOI: 10.1161/strokeaha.123.045941.

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