Analysis of convective and diffusive transport in the brain interstitium
Open Access
- 6 March 2019
- journal article
- research article
- Published by Springer Science and Business Media LLC in Fluids and Barriers of the CNS
- Vol. 16 (1), 1-18
- https://doi.org/10.1186/s12987-019-0126-9
Abstract
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. 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. 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 \(v\) = 50 μm min−1), a useful finding for researchers developing techniques to measure interstitial bulk flow. 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
Funding Information
- National Science Foundation (DMS-1361240)
This publication has 50 references indexed in Scilit:
- Interstitial fluid drainage is impaired in ischemic stroke and Alzheimer’s disease mouse modelsActa Neuropathologica, 2013
- Brain-wide pathway for waste clearance captured by contrast-enhanced MRIJCI Insight, 2013
- Extracellular sheets and tunnels modulate glutamate diffusion in hippocampal neuropilJournal of Comparative Neurology, 2012
- Diffusion in Brain Extracellular SpacePhysiological Reviews, 2008
- Solutes, but not cells, drain from the brain parenchyma along basement membranes of capillaries and arteries: significance for cerebral amyloid angiopathy and neuroimmunologyNeuropathology and Applied Neurobiology, 2008
- Penetrating arterioles are a bottleneck in the perfusion of neocortexProceedings of the National Academy of Sciences of the United States of America, 2007
- Evidence for bulk flow of brain interstitial fluid: significance for physiology and pathologyNeurochemistry International, 2004
- The role of porous media in modeling flow and heat transfer in biological tissuesInternational Journal of Heat and Mass Transfer, 2003
- Diffusion heterogeneity and anisotropy in rat hippocampusNeuroReport, 1998
- Interstitial pressure, volume, and flow during infusion into brain tissueMicrovascular Research, 1992