Modeling of brain efflux: Constraints of brain surfaces.

Proc Natl Acad Sci U S A

Center for Translational Neuromedicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200 Denmark.

Published: April 2024

Fluid efflux from the brain plays an important role in solute waste clearance. Current experimental approaches provide little spatial information, and data collection is limited due to short duration or low frequency of sampling. One approach shows tracer efflux to be independent of molecular size, indicating bulk flow, yet also decelerating like simple membrane diffusion. In an apparent contradiction to this report, other studies point to tracer efflux acceleration. We here develop a one-dimensional advection-diffusion model to gain insight into brain efflux principles. The model is characterized by nine physiological constants and three efflux parameters for which we quantify prior uncertainty. Using Bayes' rule and the two efflux studies, we validate the model and calculate data-informed parameter distributions. The apparent contradictions in the efflux studies are resolved by brain surface boundaries being bottlenecks for efflux. To critically test the model, a custom MRI efflux assay measuring solute dispersion in tissue and release to cerebrospinal fluid was employed. The model passed the test with tissue bulk flow velocities in the range 60 to 190 [Formula: see text]m/h. Dimensional analysis identified three principal determinants of efflux, highlighting brain surfaces as a restricting factor for metabolite solute clearance.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11032467PMC
http://dx.doi.org/10.1073/pnas.2318444121DOI Listing

Publication Analysis

Top Keywords

efflux
11
brain efflux
8
brain surfaces
8
tracer efflux
8
bulk flow
8
efflux studies
8
brain
5
model
5
modeling brain
4
efflux constraints
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!