Imaging the transmembrane and transendothelial sodium gradients in gliomas

Abstract Under normal conditions, high sodium (Na+) in extracellular (Na+ e) and blood (Na+ b) compartments and low Na+ in intracellular milieu (Na+ i) produce strong transmembrane (ΔNa+ mem) and weak transendothelial (ΔNa+ end) gradients respectively, and these manifest the cell membrane potential...

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Autores principales:	Muhammad H. Khan, John J. Walsh, Jelena M. Mihailović, Sandeep K. Mishra, Daniel Coman, Fahmeed Hyder
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0b22d92edfa14ae2a68ade6c68957ff3
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spelling	oai:doaj.org-article:0b22d92edfa14ae2a68ade6c68957ff32021-12-02T16:36:11ZImaging the transmembrane and transendothelial sodium gradients in gliomas10.1038/s41598-021-85925-92045-2322https://doaj.org/article/0b22d92edfa14ae2a68ade6c68957ff32021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-85925-9https://doaj.org/toc/2045-2322Abstract Under normal conditions, high sodium (Na+) in extracellular (Na+ e) and blood (Na+ b) compartments and low Na+ in intracellular milieu (Na+ i) produce strong transmembrane (ΔNa+ mem) and weak transendothelial (ΔNa+ end) gradients respectively, and these manifest the cell membrane potential (V m ) as well as blood–brain barrier (BBB) integrity. We developed a sodium (23Na) magnetic resonance spectroscopic imaging (MRSI) method using an intravenously-administered paramagnetic polyanionic agent to measure ΔNa+ mem and ΔNa+ end. In vitro 23Na-MRSI established that the 23Na signal is intensely shifted by the agent compared to other biological factors (e.g., pH and temperature). In vivo 23Na-MRSI showed Na+ i remained unshifted and Na+ b was more shifted than Na+ e, and these together revealed weakened ΔNa+ mem and enhanced ΔNa+ end in rat gliomas (vs. normal tissue). Compared to normal tissue, RG2 and U87 tumors maintained weakened ΔNa+ mem (i.e., depolarized V m ) implying an aggressive state for proliferation, whereas RG2 tumors displayed elevated ∆Na+ end suggesting altered BBB integrity. We anticipate that 23Na-MRSI will allow biomedical explorations of perturbed Na+ homeostasis in vivo.Muhammad H. KhanJohn J. WalshJelena M. MihailovićSandeep K. MishraDaniel ComanFahmeed HyderNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Muhammad H. Khan John J. Walsh Jelena M. Mihailović Sandeep K. Mishra Daniel Coman Fahmeed Hyder Imaging the transmembrane and transendothelial sodium gradients in gliomas
description	Abstract Under normal conditions, high sodium (Na+) in extracellular (Na+ e) and blood (Na+ b) compartments and low Na+ in intracellular milieu (Na+ i) produce strong transmembrane (ΔNa+ mem) and weak transendothelial (ΔNa+ end) gradients respectively, and these manifest the cell membrane potential (V m ) as well as blood–brain barrier (BBB) integrity. We developed a sodium (23Na) magnetic resonance spectroscopic imaging (MRSI) method using an intravenously-administered paramagnetic polyanionic agent to measure ΔNa+ mem and ΔNa+ end. In vitro 23Na-MRSI established that the 23Na signal is intensely shifted by the agent compared to other biological factors (e.g., pH and temperature). In vivo 23Na-MRSI showed Na+ i remained unshifted and Na+ b was more shifted than Na+ e, and these together revealed weakened ΔNa+ mem and enhanced ΔNa+ end in rat gliomas (vs. normal tissue). Compared to normal tissue, RG2 and U87 tumors maintained weakened ΔNa+ mem (i.e., depolarized V m ) implying an aggressive state for proliferation, whereas RG2 tumors displayed elevated ∆Na+ end suggesting altered BBB integrity. We anticipate that 23Na-MRSI will allow biomedical explorations of perturbed Na+ homeostasis in vivo.
format	article
author	Muhammad H. Khan John J. Walsh Jelena M. Mihailović Sandeep K. Mishra Daniel Coman Fahmeed Hyder
author_facet	Muhammad H. Khan John J. Walsh Jelena M. Mihailović Sandeep K. Mishra Daniel Coman Fahmeed Hyder
author_sort	Muhammad H. Khan
title	Imaging the transmembrane and transendothelial sodium gradients in gliomas
title_short	Imaging the transmembrane and transendothelial sodium gradients in gliomas
title_full	Imaging the transmembrane and transendothelial sodium gradients in gliomas
title_fullStr	Imaging the transmembrane and transendothelial sodium gradients in gliomas
title_full_unstemmed	Imaging the transmembrane and transendothelial sodium gradients in gliomas
title_sort	imaging the transmembrane and transendothelial sodium gradients in gliomas
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/0b22d92edfa14ae2a68ade6c68957ff3
work_keys_str_mv	AT muhammadhkhan imagingthetransmembraneandtransendothelialsodiumgradientsingliomas AT johnjwalsh imagingthetransmembraneandtransendothelialsodiumgradientsingliomas AT jelenammihailovic imagingthetransmembraneandtransendothelialsodiumgradientsingliomas AT sandeepkmishra imagingthetransmembraneandtransendothelialsodiumgradientsingliomas AT danielcoman imagingthetransmembraneandtransendothelialsodiumgradientsingliomas AT fahmeedhyder imagingthetransmembraneandtransendothelialsodiumgradientsingliomas
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Imaging the transmembrane and transendothelial sodium gradients in gliomas

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