Modeling of brain efflux: Constraints of brain surfaces
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Modeling of brain efflux : Constraints of brain surfaces. / Bork, Peter A.R.; Hauglund, Natalie L.; Mori, Yuki; Møllgård, Kjeld; Hjorth, Poul G.; Nedergaard, Maiken.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 121, No. 16, e2318444121, 2024.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Modeling of brain efflux
T2 - Constraints of brain surfaces
AU - Bork, Peter A.R.
AU - Hauglund, Natalie L.
AU - Mori, Yuki
AU - Møllgård, Kjeld
AU - Hjorth, Poul G.
AU - Nedergaard, Maiken
PY - 2024
Y1 - 2024
N2 - 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.
AB - 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.
KW - advection–diffusion
KW - glymphatics
KW - MRI
U2 - 10.1073/pnas.2318444121
DO - 10.1073/pnas.2318444121
M3 - Journal article
C2 - 38598340
AN - SCOPUS:85190562486
VL - 121
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 16
M1 - e2318444121
ER -
ID: 389553352