Interstitial solute transport in 3D reconstructed neuropil occurs by diffusion rather than bulk flow

Proceedings of the National Academy of Sciences of the United States of America

Volumn 114, Issue 37, 2017, Pages 9894-9899

  Holter, Karl Erik ^a,b   Kehlet, Benjamin ^a,b   Devor, Anna ^c,d,e   Sejnowski, Terrence J ^f,g   Dale, Anders M ^d,e   Omholt, Stig W ^h   Ottersen, Ole Petter ^a,i   Nagelhus, Erlend Arnulf ^a   Mardal, Kent André ^a,b   Pettersen, Klas H ^a  

^a UNIVERSITY OF OSLO   (Norway)

^b SIMULA RESEARCH LABORATORY   (Norway)

^c MASSACHUSETTS GENERAL HOSPITAL   (United States)

^d UNIVERSITY OF CALIFORNIA   (United States)

^e UNIVERSITY OF CALIFORNIA   (United States)

^f HOWARD HUGHES MEDICAL INSTITUTE   (United States)

^g UNIVERSITY OF CALIFORNIA SAN DIEGO   (United States)

^h NORWEGIAN UNIVERSITY OF SCIENCE AND TECHNOLOGY   (Norway)

ⁱ KAROLINSKA INSTITUTE   (Sweden)

Author keywords

AQP4; Extracellular space; Glymphatic; Interstitial fluid; Simulation

Indexed keywords

ADVECTION; ARTICLE; BULK FLOW; DIFFUSION; ELECTRON MICROSCOPE; EXTRACELLULAR SPACE; FINITE ELEMENT ANALYSIS; FLOW; FLOW RATE; HYDRAULIC CONDUCTIVITY; HYDROSTATIC PRESSURE; MEMBRANE PERMEABILITY; MOLECULAR DYNAMICS; NEUROPIL; PERIVASCULAR SPACE; PRESSURE GRADIENT; PRIORITY JOURNAL; SIMULATION; THREE DIMENSIONAL IMAGING; ANATOMY AND HISTOLOGY; ANIMAL; BLOOD BRAIN BARRIER; BODY FLUID; CEREBROSPINAL FLUID; COMPUTER SIMULATION; ELECTRON MICROSCOPY; EXTRACELLULAR FLUID; HIPPOCAMPUS; HUMAN; LYMPH VESSEL; METABOLISM; PHYSIOLOGY; TRANSPORT AT THE CELLULAR LEVEL;

ANIMALS; BIOLOGICAL TRANSPORT; BLOOD-BRAIN BARRIER; BODY FLUIDS; CEREBROSPINAL FLUID; COMPUTER SIMULATION; DIFFUSION; EXTRACELLULAR FLUID; HIPPOCAMPUS; HUMANS; IMAGING, THREE-DIMENSIONAL; LYMPHATIC VESSELS; MICROSCOPY, ELECTRON; NEUROPIL;

EID: 85029502411     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1706942114     Document Type: Article

References (35)

1. Louveau A, et al. (2015) Structural and functional features of central nervous system lymphatic vessels. Nature 523:337–341.
2. Aspelund A, et al. (2015) A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules. J Exp Med 212:991–999.
3. Smith AJ, Jin BJ, Verkman AS (2015) Muddying the water in brain edema? Trends Neurosci 38:331–332.
4. Thrane AS, Rangroo Thrane V, Plog BA, Nedergaard M (2015) Filtering the muddied waters of brain edema. Trends Neurosci 38:333–335.
5. Asgari M, de Zélicourt D, Kurtcuoglu V (2016) Glymphatic solute transport does not require bulk flow. Sci Rep 6:38635.
6. Jin BJ, Smith AJ, Verkman AS (2016) Spatial model of convective solute transport in brain extracellular space does not support a “glymphatic” mechanism. J Gen Physiol 148:489–501.
7. Abbott NJ (2004) Evidence for bulk flow of brain interstitial fluid: Significance for physiology and pathology. Neurochem Int 45:545–552.
8. Hladky SB, Barrand MA (2014) Mechanisms of fluid movement into, through and out of the brain: Evaluation of the evidence. Fluids Barriers CNS 11:26.
9. Louveau A, Da Mesquita S, Kipnis J (2016) Lymphatics in neurological disorders: A neuro-lympho-vascular component of multiple sclerosis and Alzheimer’s disease? Neuron 91:957–973.
10. Iliff JJ, et al. (2012) A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid β. Sci Transl Med 4:147.
11. Iliff JJ, et al. (2013) Cerebral arterial pulsation drives paravascular CSF-interstitial fluid exchange in the murine brain. J Neurosci 33:18190–18199.
12. Kiviniemi V, et al. (2016) Ultra-fast magnetic resonance encephalography of physiological brain activity - Glymphatic pulsation mechanisms? J Cerebr Blood Flow Metabol 36:1033–1045.
13. Cserr HF, Ostrach LH (1974) Bulk flow of interstitial fluid after intracranial injection of blue dextran 2000. Exp Neurol 45:50–60.
14. 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.
15. Tarasoff-Conway JM, et al. (2015) Clearance systems in the brain-implications for Alzheimer disease. Nat Rev Neurol 11:457–470.
16. Carare RO, et al. (2008) Solutes, but not cells, drain from the brain parenchyma along basement membranes of capillaries and arteries: Significance for cerebral amyloid angiopathy and neuroimmunology. Neuropathol Appl Neurobiol 34:131–144.
17. Morris AWJ, et al. (2016) Vascular basement membranes as pathways for the passage of fluid into and out of the brain. Acta Neuropathol 131:725–736.
18. Kinney JP, et al. (2012) Extracellular sheets and tunnels modulate glutamate diffusion in hippocampal neuropil. J Comp Neurol 521:448–464.
19. Syková E, Nicholson C (2008) Diffusion in brain extracellular space. Physiol Rev 88:1277–1340.
20. Logg A, Mardal KA, Wells G (2012) Automated Solution of Differential Equations by the Finite Element Method: The FEniCS Book, Lecture Notes in Computational Science and Engineering, eds Logg A, Mardal KA, Wells G (Springer, Berlin), Vol 84.
21. Halnes G, Østby I, Pettersen KH, Omholt SW, Einevoll GT (2013) Electrodiffusive model for astrocytic and neuronal ion concentration dynamics. PLoS Comput Biol 9:e1003386.
22. Xie L, et al. (2013) Sleep drives metabolite clearance from the adult brain. Science 342:373–377.
23. Smith JH, Humphrey JAC (2007) Interstitial transport and transvascular fluid exchange during infusion into brain and tumor tissue. Microvasc Res 73:58–73.
24. Morrison PF, Laske DW, Bobo H, Oldfield EH, Dedrick RL (1994) High-flow microinfusion: Tissue penetration and pharmacodynamics. Am J Physiol 266:R292–R305.
25. Bobo RH, et al. (1994) Convection-enhanced delivery of macromolecules in the brain. Proc Natl Acad Sci USA 91:2076–2080.
26. Prabhu SS, et al. (1998) Distribution of macromolecular dyes in brain using positive pressure infusion: A model for direct controlled delivery of therapeutic agents. Surg Neurol 50:367–375.
27. Basser PJ (1992) Interstitial pressure, volume, and flow during infusion into brain tissue. Microvasc Res 44:143–165.
28. Adams DL, Piserchia V, Economides JR, Horton JC (2015) Vascular supply of the cerebral cortex is specialized for cell layers but not columns. Cerebr Cortex 25: 3673–3681.
29. Nedergaard M (2013) Garbage truck of the brain. Science 340:1529–1530.
30. Nagelhus EA, Ottersen OP (2013) Physiological roles of aquaporin-4 in brain. Physiol Rev 93:1543–1562.
31. Nielsen S, et al. (1997) Specialized membrane domains for water transport in glial cells: High-resolution immunogold cytochemistry of aquaporin-4 in rat brain. J Neurosci 17:171–180.
32. Eide PK, Sæhle T (2010) Is ventriculomegaly in idiopathic normal pressure hydrocephalus associated with a transmantle gradient in pulsatile intracranial pressure? Acta Neurochir 152:989–995.
33. Alperin NJ, Lee SH, Loth F, Raksin PB, Lichtor T (2000) Mr-intracranial pressure (ICP): A method to measure intracranial elastance and pressure noninvasively by means of MR imaging: Baboon and human study. Radiology 217:877–885.
34. Hughes TJR, Franca LP, Balestra M (1986) A new finite element formulation for computational fluid dynamics: V. Circumventing the Babuška-Brezzi condition: A stable Petrov-Galerkin formulation of the Stokes problem accommodating equal-order interpolations. Comput Methods Appl Mech Eng 59:85–99.
35. Ahrens J, Geveci B, Law C (2005) ParaView: An end-user tool for large data visualization. Visualization Handbook, eds Hansen CD, Johnson CR (Elsevier Butterworth-Heinemann, Burlington, MA), pp 717–731.