Analysis of convective and diffusive transport in the brain interstitium

Lori Ray, Jeffrey J. Iliff, Jeffrey J. Heys

Research output: Contribution to journalArticle

15 Scopus citations

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

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Keywords

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

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience
  • Cellular and Molecular Neuroscience

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