The Glymphatic System in Central Nervous System Health and Disease: Past, Present, and Future

Annual Review of Pathology: Mechanisms of Disease

Volumn 13, Issue , 2018, Pages 379-394

  Plog, Benjamin A ^a   Nedergaard, Maiken ^a  

^a UNIVERSITY OF ROCHESTER MEDICAL CENTER   (United States)

Author keywords

Amyloid ; Aquaporin 4; Astrocyte; Cerebrospinal fluid; Glymphatic; Perivascular space

Indexed keywords

AQUAPORIN 4;

BRAIN CAPILLARY; BRAIN INTERSTITIAL FLUID; BRAIN SIZE; CENTRAL NERVOUS SYSTEM DISEASE; CEREBROSPINAL FLUID; CIRCADIAN RHYTHM; CONNECTOME; DRUG DELIVERY SYSTEM; EXTRACELLULAR SPACE; GENE THERAPY; HUMAN; NEUROPHYSIOLOGY; PERIVASCULAR SPACE; PRIORITY JOURNAL; REGULATORY MECHANISM; REVIEW; BRAIN;

BRAIN; GLYMPHATIC SYSTEM; HUMANS;

EID: 85041707837     PISSN: 15534006     EISSN: 15534014     Source Type: Book Series    
DOI: 10.1146/annurev-pathol-051217-111018     Document Type: Review

References (77)

1. Jessen NA, Munk ASF, Lundgaard I, Nedergaard M. 2015. The glymphatic system: a beginner's guide. Neurochem. Res. 40:2583-99
2. Trevaskis NL, Kaminskas LM, PorterCJH. 2015. From sewer to saviour-targeting the lymphatic system to promote drug exposure and activity. Nat. Rev. Drug Discov. 14(11):781-803
3. Oliver G. 2004. Lymphatic vasculature development. Nat. Rev. Immunol. 4(1):35-45
4. Cserr HF. 1971. Physiology of the choroid plexus. Physiol. Rev. 51(2):273-311
5. Hladky SB, Barrand MA. 2014. Mechanisms of fluid movement into, through, and out of the brain: evaluation of the evidence. Fluids Barriers CNS 11(1):26
6. Keep R, JonesH. 1990. A morphometric study on the development of the lateral ventricle choroid plexus, choroid plexus capillaries, and ventricular ependyma in the rat. Brain Res. Dev. Brain Res. 56(1):47-53
7. Maxwell D, Please D. 1956. The electron microscopy of the choroid plexus. J. Biophys. Biochem. Cytol. 2(4):467-74
8. Damkier HH, Brown PD, Praetorius J. 2013. Cerebrospinal fluid secretion by the choroid plexus. Physiol. Rev. 93(4):1847-92
9. BrightmanMW, Reese TS. 1969. Junctions between intimately apposed cell membranes in the vertebrate brain. J. Cell Biol. 40(3):648-77
10. Kratzer I, Vasiljevic A, Rey C, Fevre-Montange M, SaunderN, et al. 2012. Complexity and developmental changes in the expression pattern of claudins at the blood-CSF barrier. Histochem. Cell Biol. 138(6):861-79
11. Hladky SB, Barrand MA. 2016. Fluid and ion transfer across the blood-brain and blood-cerebrospinal fluid barriers; a comparative account of mechanisms and roles. Fluids Barriers CNS 13:19
12. Praetorius J, Nielsen S. 2006. Distribution of sodium transporters and aquaporin-1 in the human choroid plexus. Am. J. Physiol. Cell Physiol. 291(1):C59-67
13. Praetorius J. 2007. Water and solute secretion by the choroid plexus. PflugersArch. Eur. J. Physiol. 454(1):1-18
14. Vates TJ, Bonting S, OppeltW. 1964. Na-Kactivated adenosine triphosphatase formation of cerebrospinal fluid in cat. Am. J. Physiol. 206:1165-72
15. Pollay M, Hisey B, Reynolds E, Tomkins P, Stevens F, Smith R. 1985. Choroid plexusNa+/K+-activated adenosine triphosphatase and cerebrospinal fluid formation. Neurosurgery 17(5):768-72
16. Papadopoulos MC, Verkman AS. 2013. Aquaporin water channels in the nervous system. Nat. Rev. Neurosci. 14:265-77
17. Johansson P, Dziegielewska K, Ek C, Habgood M, Møllgård K, et al. 2005. Aquaporin-1 in the choroid plexuses of developing mammalian brain. Cell Tissue Res. 322(3):353-64
18. Nielsen S, Smith B, Christensen E, Agre P. 1993. Distribution of the aquaporin CHIP in secretory and resorptive epithelia and capillary endothelia. PNAS 90(15):7275-79
19. Oshio K, Song Y, Verkman A, ManleyG. 2003. Aquaporin-1 deletion reduces osmotic water permeability and cerebrospinal fluid production. Acta Neurochir. Suppl. 86:525-28
20. Oshio K, Watanabe H, Song Y, Verkman A, ManleyG. 2005. Reduced cerebrospinal fluid production and intracranial pressure in mice lacking choroid plexus water channel Aquaporin-1. FASEB J. 19(1):76-78
21. Stokum JA, Gerzanich V, Simard JM. 2016. Molecular pathophysiology of cerebral edema. J. Cereb. Blood Flow Metab. 36(3):513-38
22. Farrell C, Yang J, PardridgeW. 1992. GLUT-1glucose transporter is present within apical and basolateral membranes of brain epithelial interfaces and in microvascular endothelia with and without tight junctions. J. Histochem. Cytochem. 40(2):193-99
23. Fischbarg J, Kuang K, Hirsch J, Lecuona S, RogozinskiL, et al. 1989. Evidence that the glucose transporter serves as a water channel in J774 macrophages. PNAS 86(21):8397-401
24. Fischbarg J, Kuang K, Vera J, Arant S, Silverstein S, et al. 1990. Glucose transporters serve as water channels. PNAS 87(8):3244-47
25. Cserr HF, Ostrach LH. 1974. Bulk flow of interstitial fluid after intracranial injection of Blue Dextran 2000. Exp. Neurol. 45(1):50-60
26. Cserr HF, Cooper DN, Milhorat TH. 1977. Flow of cerebral interstitial fluid as indicated by the removal of extracellular markers from rat caudate nucleus. Exp. Eye Res. 25(Suppl.):461-73
27. Szentistvanyi I, Patlak CS, Ellis RA, Cserr HF. 1984. Drainage of interstitial fluid from different regions of rat brain. Am. J. Physiol. Ren. Physiol. 246:F835-44
28. Ball KK, Cruz NF, Mrak RE, Dienel GA. 2010. Trafficking of glucose, lactate, and amyloid-?from the inferior colliculus through perivascular routes. J. Cereb. Blood Flow Metab. 30(1):162-76
29. Thrane AS, Rangroo Thrane V, Nedergaard M. 2014. Drowning stars: reassessing the role of astrocytes in brain edema. Trends Neurosci. 37:620-28
30. CserrHF, CooperDN, Suri PK, Patlak CS. 1981. Efflux of radiolabeled polyethylene glycols and albumin from rat brain. Am. J. Physiol. Ren. Physiol. 240:F319-28
31. Abbott NJ. 2004. Evidence for bulk flow of brain interstitial fluid: significance for physiology and pathology. Neurochem. Int. 45(4):545-52
32. Rennels ML, Gregory TF, Blaumanis OR, Fujimoto K, Grady PA. 1985. Evidence for a "paravascular" fluid circulation in the mammalian central nervous system, provided by the rapid distribution of tracer protein throughout the brain from the subarachnoid space. Brain Res. 326:47-63
33. Rennels ML, BlaumanisOR, Grady PA. 1990. Rapid solute transport throughout the brain via paravascular fluid pathways. Adv. Neurol. 52:431-39
34. Blaumanis OR, Rennels ML, Grady PA. 1990. Focal cerebral edema impedes convective fluid/tracer movement through paravascular pathways in cat brain. Adv. Neurol. 52:385-89
35. Ichimura T, Fraser PA, Cserr HF. 1991. Distribution of extracellular tracers in perivascular spaces of the rat brain. Brain Res. 545(1-2):103-13
36. Iliff JJ, Wang M, Liao Y, Plogg BA, Peng W, et al. 2012. A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid ?. Sci. Transl. Med. 4(147):147ra111
37. Nagelhus EA, Ottersen OP. 2013. Physiological roles of aquaporin-4 in brain. Physiol. Rev. 93(4):1543-62
38. Weed L. 1914. Studies on cerebro-spinal fluid. No. III: the pathways of escape from the subarachnoid spaces with particular reference to the arachnoid villi. J. Med. Res. 31(1):51-91
39. Lee H, Xie L, Yu M, Kang H, Feng T, et al. 2015. The effect of body posture on brain glymphatic transport. J. Neurosci. 35(31):11034-44
40. Iliff JJ, Lee H, Yu M, Feng T, Logan J, et al. 2013. Brain-wide pathway for waste clearance captured by contrast-enhanced MRI. J. Clin. Investig. 123(3):1299-309
41. BradburyMWB, Cole DF. 1980. The role of the lymphatic system in drainage of cerebrospinal fluid and aqueous humour. J. Physiol. 299:353-65
42. Bradbury MW, Westrop RJ. 1983. Factors influencing exit of substances from cerebrospinal fluid into deep cervical lymph of the rabbit. J. Physiol. 339:519-34
43. Bradbury MW, Cserr HF, Westrop RJ. 1981. Drainage of cerebral interstitial fluid into deep cervical lymph of the rabbit. Am. J. Physiol. Ren. Physiol. 240:F329-36
44. Yamada S, DePasquale M, Patlak CS, Cserr HF. 1991. Albumin outflow into deep cervical lymph from different regions of rabbit brain. Am. J. Physiol. Circ. Physiol. 261:H1197-204
45. Mathieu E, Gupta N, Macdonald RL, Ai J, Yucel YH. 2013. In vivo imaging of lymphatic drainage of cerebrospinal fluid in mouse. Fluids Barriers CNS 10:35
46. Johnston M, Zakharov A, Papaiconomou C, Salmasi G, Armstrong D. 2004. Evidence of connections between cerebrospinal fluid and nasal lymphatic vessels in humans, non-human primates and other mammalian species. Cerebrospinal Fluid Res. 1(1):2
47. Louveau A, Smirnov I, Keyes TJ, Eccles JD, Rouhani SJ, et al. 2015. Structural and functional features of central nervous system lymphatic vessels. Nature 523(7560):337-41
48. Aspelund A, Antila S, Proulx ST, Karlsen TV, Karaman S, et al. 2015. A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules. J. Exp. Med. 212(7):991-99
49. RaperD, Louveau A, Kipnis J. 2016. How domeningeal lymphatic vessels drain theCNS? TrendsNeurosci. 39(9):581-86
50. Iliff JJ, Wang M, Zeppenfeld DM, Venkataraman A, Plog BA, et al. 2013. Cerebral arterial pulsation drives paravascular CSF-interstitial fluid exchange in the murine brain. J. Neurosci. 33(46):18190-99
51. Kiviniemi V, Wang X, Korhonen V, Keinänen T, Tuovinen T, et al. 2015. Ultra-fast magnetic resonance encephalography of physiological brain activity-glymphatic pulsation mechanisms? J. Cereb. Blood Flow Metab. 36:1033-45
52. Xie L, Kang H, Xu Q, Chen MJ, Liao Y, et al. 2013. Sleep drives metabolite clearance from the adult brain. Science 342(6156):373-77
53. Lundgaard I, Lu ML, Yang E, Peng W, Mestre H, et al. 2017. Glymphatic clearance controls statedependent changes in brain lactate concentration. J. Cereb. Blood Flow Metab. 37:2112-24
54. Lundgaard I, Li B, Xie L, Kang H, Sanggaard S, et al. 2015. Direct neuronal glucose uptake heralds activity-dependent increases in cerebral metabolism. Nat. Commun. 6:6807
55. Murlidharan G, Crowther A, Reardon RA, Song J, Asokan A. 2016. Glymphatic fluid transport controls paravascular clearance of AAV vectors from the brain. JCI Insight 1(14):e88034
56. Thrane VR, Thrane AS, Plog BA, Thiyagarajan M, Iliff JJ, et al. 2013. Paravascular microcirculation facilitates rapid lipid transport and astrocyte signaling in the brain. Sci. Rep. 3:2582
57. Maneshi MM, Maki B, Gnanasambandam R, Belin S, PopescuGK, et al. 2017. Mechanical stress activates NMDA receptors in the absence of agonists. Sci. Rep. 7:39610
58. Kress BT, Iliff JJ, Xia M, Wang M, Wei H, et al. 2014. Impairment of paravascular clearance pathways in the aging brain. Ann. Neurol. 76:845-61
59. Peng W, Achariyar TM, Li B, Liao Y, Mestre H, et al. 2016. Suppression of glymphatic fluid transport in a mouse model of Alzheimer's disease. Neurobiol. Dis. 93:215-25
60. Gaberel T, Gakuba C, Goulay R, Martinez De Lizarrondo S, Hanouz J-L, et al. 2014. Impaired glymphatic perfusion after strokes revealed by contrast-enhanced MRI: a new target for fibrinolysis? Stroke 45(10):3092-96
61. Wang M, Ding F, Deng S, Guo X, Wang W, et al. 2017. Focal solute trapping and global glymphatic pathway impairment in a murine model of multiple microinfarcts. J. Neurosci. 37:2870-77
62. Iliff JJ, Chen MJ, Plog BA, Zeppenfeld DM, Soltero M, et al. 2014. Impairment of glymphatic pathway function promotes tau pathology after traumatic brain injury. J. Neurosci. 34(49):16180-93
63. JiangQ, Zhang L, Ding G, Davoodi-Bojd E, LiQ, et al. 2017. Impairment of the glymphatic system after diabetes. J. Cereb. Blood Flow Metab. 37:1326-37
64. BrightmanM. 1992. Ultrastructure of brain endothelium. In Physiology and Pharmacology of the Blood-Brain Barrier, ed. MWB Bradbury, pp. 1-22. Berlin/Heidelberg: Springer-Verlag
65. Oldendorf W, Cornford M, Brown W. 1977. The large apparent work capability of the blood-brain barrier: a study of the mitochondrial content of capillary endothelial cells in brain and other tissues of the rat. Ann. Neurol. 1(5):409-17
66. Haj-Yasein NN, Vindedal GF, Eilert-Olsen M, Gundersen GA, Skare O, et al. 2011. Glial-conditional deletion of aquaporin-4 (Aqp4) reduces blood-brain water uptake and confers barrier function on perivascular astrocyte endfeet. PNAS 108(43):17815-20
67. CserrHF. 1988. Role of secretion and bulk flow of brain interstitial fluid in brain volume regulation. Ann. N. Y. Acad. Sci. 529(1):9-20
68. Raichle ME, Hartman BK, Eichling JO, Sharpe LG. 1975. Central noradrenergic regulation of cerebral blood flow and vascular permeability. PNAS 72(9):3726-30
69. Harik SI. 1986. Blood-brain barrier sodium/potassium pump: modulation by central noradrenergic innervation. PNAS 83(11):4067-70
70. Raichle ME, Grubb RL. 1978. Regulation of brain water permeability by centrally-released vasopressin. Brain Res. 143(1):191-94
71. Doczi T, Szerdahelyi P, Gulya K, Kiss J. 1982. Brain water accumulation after the central administration of vasopressin. Neurosurgery 11(3):402-7
72. Krieg SM, Sonanini S, Plesnila N, Trabold R. 2015. Effect of small molecule vasopressin V1a and V2 receptor antagonists on brain edema formation and secondary brain damage following traumatic brain injury in mice. J. Neurotrauma 32:221-27
73. Zarow C, Lyness SA, Mortimer JA, Chui HC. 2003. Neuronal loss is greater in the locus coeruleus than nucleus basalis and substantia nigra in Alzheimer and Parkinson diseases. Arch. Neurol. 60(3):337-41
74. RaskindMA, Peskind ER, Halter JB, Jimerson DC. 1984. Norepinephrine andMHPG levels in CSF and plasma in Alzheimer's disease. Arch. Gen. Psychiatry 41(4):343-46
75. Vulchanova L, Schuster DJ, Belur LR, Riedl MS, Podetz-Pedersen KM, et al. 2010. Differential adenoassociated virus mediated gene transfer to sensory neurons following intrathecal delivery by direct lumbar puncture. Mol. Pain 6:31
76. Yang L, Kress BT, Weber HJ, Thiyagarajan M, Wang B, et al. 2013. Evaluating glymphatic pathway function utilizing clinically relevant intrathecal infusion of CSF tracer. J. Transl. Med. 11:107
77. Nedergaard M. 2013. Garbage truck of the brain. Science 340(6140):1529-30