Estimates of the Permeability of Extra-cellular Pathways Through the Astrocyte Endfoot Sheath

Overview

Journal Fluids Barriers CNS

Publisher Biomed Central

Date 2023 Mar 21

PMID 36941607

Authors

Timo Koch

Vegard Vinje

Kent-Andre Mardal

Affiliations

Soon will be listed here.

Abstract

Background: Astrocyte endfoot processes are believed to cover all micro-vessels in the brain cortex and may play a significant role in fluid and substance transport into and out of the brain parenchyma. Detailed fluid mechanical models of diffusive and advective transport in the brain are promising tools to investigate theories of transport.

Methods: We derive theoretical estimates of astrocyte endfoot sheath permeability for advective and diffusive transport and its variation in microvascular networks from mouse brain cortex. The networks are based on recently published experimental data and generated endfoot patterns are based on Voronoi tessellations of the perivascular surface. We estimate corrections for projection errors in previously published data.

Results: We provide structural-functional relationships between vessel radius and resistance that can be directly used in flow and transport simulations. We estimate endfoot sheath filtration coefficients in the range [Formula: see text] to [Formula: see text], diffusion membrane coefficients for small solutes in the range [Formula: see text] to [Formula: see text], and gap area fractions in the range 0.2-0.6%, based on a inter-endfoot gap width of 20 nm.

Conclusions: The astrocyte endfoot sheath surrounding microvessels forms a secondary barrier to extra-cellular transport, separating the extra-cellular space of the parenchyma and the perivascular space outside the endothelial layer. The filtration and membrane diffusion coefficients of the endfoot sheath are estimated to be an order of magnitude lower than those of the extra-cellular matrix while being two orders of magnitude higher than those of the vessel wall.

Citing Articles

Directional flow in perivascular networks: mixed finite elements for reduced-dimensional models on graphs.

Gjerde I, Kuchta M, Rognes M, Wohlmuth B J Math Biol. 2024; 89(6):60.

PMID: 39511029 PMC: 11543763. DOI: 10.1007/s00285-024-02154-0.

A brain-wide solute transport model of the glymphatic system.

Quirk K, Boster K, Tithof J, Kelley D J R Soc Interface. 2024; 21(219):20240369.

PMID: 39439312 PMC: 11496954. DOI: 10.1098/rsif.2024.0369.

Modeling CSF circulation and the glymphatic system during infusion using subject specific intracranial pressures and brain geometries.

Dreyer L, Eklund A, Rognes M, Malm J, Qvarlander S, Stoverud K Fluids Barriers CNS. 2024; 21(1):82.

PMID: 39407250 PMC: 11481529. DOI: 10.1186/s12987-024-00582-0.

Simulating the impact of tumor mechanical forces on glymphatic networks in the brain parenchyma.

Siri S, Burchett A, Datta M Biomech Model Mechanobiol. 2024; 23(6):2229-2241.

PMID: 39298038 PMC: 11554883. DOI: 10.1007/s10237-024-01890-y.

Microglia contact cerebral vasculature through gaps between astrocyte endfeet.

Morris G, Foster C, Sutherland B, Grubb S J Cereb Blood Flow Metab. 2024; 44(12):1472-1486.

PMID: 39253821 PMC: 11751324. DOI: 10.1177/0271678X241280775.

References

Koch T, Flemisch B, Helmig R, Wiest R, Obrist D . A multiscale subvoxel perfusion model to estimate diffusive capillary wall conductivity in multiple sclerosis lesions from perfusion MRI data. Int J Numer Method Biomed Eng. 2019; 36(2):e3298. DOI: 10.1002/cnm.3298. View

McCaslin A, Chen B, Radosevich A, Cauli B, Hillman E . In vivo 3D morphology of astrocyte-vasculature interactions in the somatosensory cortex: implications for neurovascular coupling. J Cereb Blood Flow Metab. 2010; 31(3):795-806. PMC: 3063633. DOI: 10.1038/jcbfm.2010.204. View

Asgari M, de Zelicourt D, Kurtcuoglu V . How astrocyte networks may contribute to cerebral metabolite clearance. Sci Rep. 2015; 5:15024. PMC: 4604494. DOI: 10.1038/srep15024. View

Vinje V, Eklund A, Mardal K, Rognes M, Stoverud K . Intracranial pressure elevation alters CSF clearance pathways. Fluids Barriers CNS. 2020; 17(1):29. PMC: 7161287. DOI: 10.1186/s12987-020-00189-1. View

Blinder P, Tsai P, Kaufhold J, Knutsen P, Suhl H, Kleinfeld D . The cortical angiome: an interconnected vascular network with noncolumnar patterns of blood flow. Nat Neurosci. 2013; 16(7):889-97. PMC: 4141079. DOI: 10.1038/nn.3426. View

Hladky S, Barrand M . The glymphatic hypothesis: the theory and the evidence. Fluids Barriers CNS. 2022; 19(1):9. PMC: 8815211. DOI: 10.1186/s12987-021-00282-z. View

Watanabe K, Takeishi H, Hayakawa T, Sasaki H . Three-dimensional organization of the perivascular glial limiting membrane and its relationship with the vasculature: a scanning electron microscope study. Okajimas Folia Anat Jpn. 2010; 87(3):109-21. DOI: 10.2535/ofaj.87.109. View

Keller D, Ero C, Markram H . Cell Densities in the Mouse Brain: A Systematic Review. Front Neuroanat. 2018; 12:83. PMC: 6205984. DOI: 10.3389/fnana.2018.00083. View

Eide P, Valnes L, Lindstrom E, Mardal K, Ringstad G . Direction and magnitude of cerebrospinal fluid flow vary substantially across central nervous system diseases. Fluids Barriers CNS. 2021; 18(1):16. PMC: 8017867. DOI: 10.1186/s12987-021-00251-6. View

10.

Faghih M, Sharp M . Is bulk flow plausible in perivascular, paravascular and paravenous channels?. Fluids Barriers CNS. 2018; 15(1):17. PMC: 6003203. DOI: 10.1186/s12987-018-0103-8. View

11.

Swabb E, Wei J, Gullino P . Diffusion and convection in normal and neoplastic tissues. Cancer Res. 1974; 34(10):2814-22. View

12.

Korogod N, Petersen C, Knott G . Ultrastructural analysis of adult mouse neocortex comparing aldehyde perfusion with cryo fixation. Elife. 2015; 4. PMC: 4530226. DOI: 10.7554/eLife.05793. View

13.

Hill R, Tong L, Yuan P, Murikinati S, Gupta S, Grutzendler J . Regional Blood Flow in the Normal and Ischemic Brain Is Controlled by Arteriolar Smooth Muscle Cell Contractility and Not by Capillary Pericytes. Neuron. 2015; 87(1):95-110. PMC: 4487786. DOI: 10.1016/j.neuron.2015.06.001. View

14.

Ji X, Ferreira T, Friedman B, Liu R, Liechty H, Bas E . Brain microvasculature has a common topology with local differences in geometry that match metabolic load. Neuron. 2021; 109(7):1168-1187.e13. PMC: 8525211. DOI: 10.1016/j.neuron.2021.02.006. View

15.

MacAulay N . Molecular mechanisms of brain water transport. Nat Rev Neurosci. 2021; 22(6):326-344. DOI: 10.1038/s41583-021-00454-8. View

16.

Michel C, Curry F . Microvascular permeability. Physiol Rev. 1999; 79(3):703-61. DOI: 10.1152/physrev.1999.79.3.703. View

17.

Honda H . Description of cellular patterns by Dirichlet domains: the two-dimensional case. J Theor Biol. 1978; 72(3):523-43. DOI: 10.1016/0022-5193(78)90315-6. View

18.

Zisis E, Keller D, Kanari L, Arnaudon A, Gevaert M, Delemontex T . Digital Reconstruction of the Neuro-Glia-Vascular Architecture. Cereb Cortex. 2021; 31(12):5686-5703. PMC: 8568010. DOI: 10.1093/cercor/bhab254. View

19.

Brightman M, Reese T . Junctions between intimately apposed cell membranes in the vertebrate brain. J Cell Biol. 1969; 40(3):648-77. PMC: 2107650. DOI: 10.1083/jcb.40.3.648. View

20.

Beck R, Schultz J . Hindrance of solute diffusion within membranes as measured with microporous membranes of known pore geometry. Biochim Biophys Acta. 1972; 255(1):273-303. DOI: 10.1016/0005-2736(72)90028-4. View