A real-time in vivo clearance assay for quantification of glymphatic efflux

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

A real-time in vivo clearance assay for quantification of glymphatic efflux. / Plá, Virginia; Bork, Peter; Harnpramukkul, Aurakoch; Olveda, Genaro; Ladrón-de-Guevara, Antonio; Giannetto, Michael J.; Hussain, Rashad; Wang, Wei; Kelley, Douglas H.; Hablitz, Lauren M.; Nedergaard, Maiken.

In: Cell Reports, Vol. 40, No. 11, 111320, 2022.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Plá, V, Bork, P, Harnpramukkul, A, Olveda, G, Ladrón-de-Guevara, A, Giannetto, MJ, Hussain, R, Wang, W, Kelley, DH, Hablitz, LM & Nedergaard, M 2022, 'A real-time in vivo clearance assay for quantification of glymphatic efflux', Cell Reports, vol. 40, no. 11, 111320. https://doi.org/10.1016/j.celrep.2022.111320

APA

Plá, V., Bork, P., Harnpramukkul, A., Olveda, G., Ladrón-de-Guevara, A., Giannetto, M. J., Hussain, R., Wang, W., Kelley, D. H., Hablitz, L. M., & Nedergaard, M. (2022). A real-time in vivo clearance assay for quantification of glymphatic efflux. Cell Reports, 40(11), [111320]. https://doi.org/10.1016/j.celrep.2022.111320

Vancouver

Plá V, Bork P, Harnpramukkul A, Olveda G, Ladrón-de-Guevara A, Giannetto MJ et al. A real-time in vivo clearance assay for quantification of glymphatic efflux. Cell Reports. 2022;40(11). 111320. https://doi.org/10.1016/j.celrep.2022.111320

Author

Plá, Virginia ; Bork, Peter ; Harnpramukkul, Aurakoch ; Olveda, Genaro ; Ladrón-de-Guevara, Antonio ; Giannetto, Michael J. ; Hussain, Rashad ; Wang, Wei ; Kelley, Douglas H. ; Hablitz, Lauren M. ; Nedergaard, Maiken. / A real-time in vivo clearance assay for quantification of glymphatic efflux. In: Cell Reports. 2022 ; Vol. 40, No. 11.

Bibtex

@article{54ffd3062a784df3bb520a15a8fc4153,
title = "A real-time in vivo clearance assay for quantification of glymphatic efflux",
abstract = "Glymphatic fluid transport eliminates metabolic waste from the brain including amyloid-β, yet the methodology for studying efflux remains rudimentary. Here, we develop a method to evaluate glymphatic real-time clearance. Efflux of Direct Blue 53 (DB53, also T-1824 or Evans Blue) injected into the striatum is quantified by imaging the DB53 signal in the vascular compartment, where it is retained due to its high affinity to albumin. The DB53 signal is detectable as early as 15 min after injection and the efflux kinetics are sharply reduced in mice lacking the water channel aquaporin 4 (AQP4). Pharmacokinetic modeling reveal that DB53 efflux is consistent with the existence of two efflux paths, one with fast kinetics (T1/2 = 50 min) and another with slow kinetics (T1/2 = 240 min), in wild-type mice. This in vivo methodology will aid in defining the physiological variables that drive efflux, as well as the impact of brain states or disorders on clearance kinetics.",
keywords = "aquaporin 4, brain clearance, brain fluid transport, cerebrospinal fluid, CP: Neuroscience, glymphatic system, waste efflux",
author = "Virginia Pl{\'a} and Peter Bork and Aurakoch Harnpramukkul and Genaro Olveda and Antonio Ladr{\'o}n-de-Guevara and Giannetto, {Michael J.} and Rashad Hussain and Wei Wang and Kelley, {Douglas H.} and Hablitz, {Lauren M.} and Maiken Nedergaard",
note = "Publisher Copyright: {\textcopyright} 2022",
year = "2022",
doi = "10.1016/j.celrep.2022.111320",
language = "English",
volume = "40",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "11",

}

RIS

TY - JOUR

T1 - A real-time in vivo clearance assay for quantification of glymphatic efflux

AU - Plá, Virginia

AU - Bork, Peter

AU - Harnpramukkul, Aurakoch

AU - Olveda, Genaro

AU - Ladrón-de-Guevara, Antonio

AU - Giannetto, Michael J.

AU - Hussain, Rashad

AU - Wang, Wei

AU - Kelley, Douglas H.

AU - Hablitz, Lauren M.

AU - Nedergaard, Maiken

N1 - Publisher Copyright: © 2022

PY - 2022

Y1 - 2022

N2 - Glymphatic fluid transport eliminates metabolic waste from the brain including amyloid-β, yet the methodology for studying efflux remains rudimentary. Here, we develop a method to evaluate glymphatic real-time clearance. Efflux of Direct Blue 53 (DB53, also T-1824 or Evans Blue) injected into the striatum is quantified by imaging the DB53 signal in the vascular compartment, where it is retained due to its high affinity to albumin. The DB53 signal is detectable as early as 15 min after injection and the efflux kinetics are sharply reduced in mice lacking the water channel aquaporin 4 (AQP4). Pharmacokinetic modeling reveal that DB53 efflux is consistent with the existence of two efflux paths, one with fast kinetics (T1/2 = 50 min) and another with slow kinetics (T1/2 = 240 min), in wild-type mice. This in vivo methodology will aid in defining the physiological variables that drive efflux, as well as the impact of brain states or disorders on clearance kinetics.

AB - Glymphatic fluid transport eliminates metabolic waste from the brain including amyloid-β, yet the methodology for studying efflux remains rudimentary. Here, we develop a method to evaluate glymphatic real-time clearance. Efflux of Direct Blue 53 (DB53, also T-1824 or Evans Blue) injected into the striatum is quantified by imaging the DB53 signal in the vascular compartment, where it is retained due to its high affinity to albumin. The DB53 signal is detectable as early as 15 min after injection and the efflux kinetics are sharply reduced in mice lacking the water channel aquaporin 4 (AQP4). Pharmacokinetic modeling reveal that DB53 efflux is consistent with the existence of two efflux paths, one with fast kinetics (T1/2 = 50 min) and another with slow kinetics (T1/2 = 240 min), in wild-type mice. This in vivo methodology will aid in defining the physiological variables that drive efflux, as well as the impact of brain states or disorders on clearance kinetics.

KW - aquaporin 4

KW - brain clearance

KW - brain fluid transport

KW - cerebrospinal fluid

KW - CP: Neuroscience

KW - glymphatic system

KW - waste efflux

U2 - 10.1016/j.celrep.2022.111320

DO - 10.1016/j.celrep.2022.111320

M3 - Journal article

C2 - 36103828

AN - SCOPUS:85138108547

VL - 40

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 11

M1 - 111320

ER -

ID: 343131000