Imaging the transmembrane and transendothelial sodium gradients in gliomas

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 potent...

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Bibliographic Details
Published in:Scientific reports 2021-03, Vol.11 (1), p.6710-6710, Article 6710
Main Authors: Khan, Muhammad H., Walsh, John J., Mihailović, Jelena M., Mishra, Sandeep K., Coman, Daniel, Hyder, Fahmeed
Format: Article
Language:English
Subjects:
631/378/1341
631/67/1857
631/67/1922
631/67/2321
631/67/2327
631/67/2329
631/67/327
Biomarkers
Blood-brain barrier
Brain cancer
Cell cycle
Cell membranes
Glioma
Homeostasis
Humanities and Social Sciences
Magnetic resonance imaging
Magnetic resonance spectroscopy
Membrane potential
multidisciplinary
Neuroimaging
NMR
Nuclear magnetic resonance
Science
Science (multidisciplinary)
Sodium
Tumors
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Summary: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 ( 23 Na) magnetic resonance spectroscopic imaging (MRSI) method using an intravenously-administered paramagnetic polyanionic agent to measure ΔNa + mem and ΔNa + end . In vitro 23 Na-MRSI established that the 23 Na signal is intensely shifted by the agent compared to other biological factors (e.g., pH and temperature). In vivo 23 Na-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 23 Na-MRSI will allow biomedical explorations of perturbed Na + homeostasis in vivo.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-021-85925-9