Analysis of convective and diffusive transport in the brain interstitium

Lori Ray, Jeffrey Iliff, Jeffrey J. Heys

Research output: Contribution to journalArticle

Abstract

Background: Despite advances in in vivo imaging and experimental techniques, the nature of transport mechanisms in the brain remain elusive. Mathematical modelling verified using available experimental data offers a powerful tool for investigating hypotheses regarding extracellular transport of molecules in brain tissue. Here we describe a tool developed to aid in investigation of interstitial transport mechanisms, especially the potential for convection (or bulk flow) and its relevance to interstitial solute transport, for which there is conflicting evidence. Methods: In this work, we compare a large body of published experimental data for transport in the brain to simulations of purely diffusive transport and simulations of combined convective and diffusive transport in the brain interstitium, incorporating current theories of perivascular influx and efflux. Results: The simulations show (1) convective flow in the interstitium potentially of a similar magnitude to diffusive transport for molecules of interest and (2) exchange between the interstitium and perivascular space, whereby fluid and solutes may enter or exit the interstitium, are consistent with the experimental data. Simulations provide an upper limit for superficial convective velocity magnitude (approximately v v = 50 μm min -1 ), a useful finding for researchers developing techniques to measure interstitial bulk flow. Conclusions: For the large molecules of interest in neuropathology, bulk flow may be an important mechanism of interstitial transport. Further work is warranted to investigate the potential for bulk flow.

Original languageEnglish (US)
Article number6
JournalFluids and Barriers of the CNS
Volume16
Issue number1
DOIs
StatePublished - Mar 6 2019

Fingerprint

Brain
Convection
Research Personnel
Neuropathology

Keywords

  • Biotransport
  • Bulk flow
  • Finite element model
  • Parenchyma
  • Real time iontophoresis

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience
  • Cellular and Molecular Neuroscience

Cite this

Analysis of convective and diffusive transport in the brain interstitium. / Ray, Lori; Iliff, Jeffrey; Heys, Jeffrey J.

In: Fluids and Barriers of the CNS, Vol. 16, No. 1, 6, 06.03.2019.

Research output: Contribution to journalArticle

@article{922ac251138e493d8d905911f61fbe8c,
title = "Analysis of convective and diffusive transport in the brain interstitium",
abstract = "Background: Despite advances in in vivo imaging and experimental techniques, the nature of transport mechanisms in the brain remain elusive. Mathematical modelling verified using available experimental data offers a powerful tool for investigating hypotheses regarding extracellular transport of molecules in brain tissue. Here we describe a tool developed to aid in investigation of interstitial transport mechanisms, especially the potential for convection (or bulk flow) and its relevance to interstitial solute transport, for which there is conflicting evidence. Methods: In this work, we compare a large body of published experimental data for transport in the brain to simulations of purely diffusive transport and simulations of combined convective and diffusive transport in the brain interstitium, incorporating current theories of perivascular influx and efflux. Results: The simulations show (1) convective flow in the interstitium potentially of a similar magnitude to diffusive transport for molecules of interest and (2) exchange between the interstitium and perivascular space, whereby fluid and solutes may enter or exit the interstitium, are consistent with the experimental data. Simulations provide an upper limit for superficial convective velocity magnitude (approximately v v = 50 μm min -1 ), a useful finding for researchers developing techniques to measure interstitial bulk flow. Conclusions: For the large molecules of interest in neuropathology, bulk flow may be an important mechanism of interstitial transport. Further work is warranted to investigate the potential for bulk flow.",
keywords = "Biotransport, Bulk flow, Finite element model, Parenchyma, Real time iontophoresis",
author = "Lori Ray and Jeffrey Iliff and Heys, {Jeffrey J.}",
year = "2019",
month = "3",
day = "6",
doi = "10.1186/s12987-019-0126-9",
language = "English (US)",
volume = "16",
journal = "Fluids and Barriers of the CNS",
issn = "2045-8118",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - Analysis of convective and diffusive transport in the brain interstitium

AU - Ray, Lori

AU - Iliff, Jeffrey

AU - Heys, Jeffrey J.

PY - 2019/3/6

Y1 - 2019/3/6

N2 - Background: Despite advances in in vivo imaging and experimental techniques, the nature of transport mechanisms in the brain remain elusive. Mathematical modelling verified using available experimental data offers a powerful tool for investigating hypotheses regarding extracellular transport of molecules in brain tissue. Here we describe a tool developed to aid in investigation of interstitial transport mechanisms, especially the potential for convection (or bulk flow) and its relevance to interstitial solute transport, for which there is conflicting evidence. Methods: In this work, we compare a large body of published experimental data for transport in the brain to simulations of purely diffusive transport and simulations of combined convective and diffusive transport in the brain interstitium, incorporating current theories of perivascular influx and efflux. Results: The simulations show (1) convective flow in the interstitium potentially of a similar magnitude to diffusive transport for molecules of interest and (2) exchange between the interstitium and perivascular space, whereby fluid and solutes may enter or exit the interstitium, are consistent with the experimental data. Simulations provide an upper limit for superficial convective velocity magnitude (approximately v v = 50 μm min -1 ), a useful finding for researchers developing techniques to measure interstitial bulk flow. Conclusions: For the large molecules of interest in neuropathology, bulk flow may be an important mechanism of interstitial transport. Further work is warranted to investigate the potential for bulk flow.

AB - Background: Despite advances in in vivo imaging and experimental techniques, the nature of transport mechanisms in the brain remain elusive. Mathematical modelling verified using available experimental data offers a powerful tool for investigating hypotheses regarding extracellular transport of molecules in brain tissue. Here we describe a tool developed to aid in investigation of interstitial transport mechanisms, especially the potential for convection (or bulk flow) and its relevance to interstitial solute transport, for which there is conflicting evidence. Methods: In this work, we compare a large body of published experimental data for transport in the brain to simulations of purely diffusive transport and simulations of combined convective and diffusive transport in the brain interstitium, incorporating current theories of perivascular influx and efflux. Results: The simulations show (1) convective flow in the interstitium potentially of a similar magnitude to diffusive transport for molecules of interest and (2) exchange between the interstitium and perivascular space, whereby fluid and solutes may enter or exit the interstitium, are consistent with the experimental data. Simulations provide an upper limit for superficial convective velocity magnitude (approximately v v = 50 μm min -1 ), a useful finding for researchers developing techniques to measure interstitial bulk flow. Conclusions: For the large molecules of interest in neuropathology, bulk flow may be an important mechanism of interstitial transport. Further work is warranted to investigate the potential for bulk flow.

KW - Biotransport

KW - Bulk flow

KW - Finite element model

KW - Parenchyma

KW - Real time iontophoresis

UR - http://www.scopus.com/inward/record.url?scp=85062496999&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85062496999&partnerID=8YFLogxK

U2 - 10.1186/s12987-019-0126-9

DO - 10.1186/s12987-019-0126-9

M3 - Article

VL - 16

JO - Fluids and Barriers of the CNS

JF - Fluids and Barriers of the CNS

SN - 2045-8118

IS - 1

M1 - 6

ER -