Spreading depolarizations trigger caveolin-1-dependent endothelial transcytosis

Annals of Neurology
Homa SadeghianCenk Ayata

Abstract

Cortical spreading depolarizations (CSDs) are intense and ubiquitous depolarization waves relevant for the pathophysiology of migraine and brain injury. CSDs disrupt the blood-brain barrier (BBB), but the mechanisms are unknown. A total of six CSDs were evoked over 1 hour by topical application of 300 mM of KCl or optogenetically with 470 nm (blue) LED over the right hemisphere in anesthetized mice (C57BL/6 J wild type, Thy1-ChR2-YFP line 18, and cav-1-/- ). BBB disruption was assessed by Evans blue (2% EB, 3 ml/kg, intra-arterial) or dextran (200 mg/kg, fluorescein, 70,000 MW, intra-arterial) extravasation in parietotemporal cortex at 3 to 24 hours after CSD. Endothelial cell ultrastructure was examined using transmission electron microscopy 0 to 24 hours after the same CSD protocol in order to assess vesicular trafficking, endothelial tight junctions, and pericyte integrity. Mice were treated with vehicle, isoform nonselective rho-associated kinase (ROCK) inhibitor fasudil (10 mg/kg, intraperitoneally 30 minutes before CSD), or ROCK-2 selective inhibitor KD025 (200 mg/kg, per oral twice-daily for 5 doses before CSD). We show that CSD-induced BBB opening to water and large molecules is mediated by increased endothelial transcy...Continue Reading

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Citations

Jul 12, 2019·Translational Stroke Research·Jyoti GautamYao Yao
Sep 17, 2020·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Paul FischerCenk Ayata
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Apr 24, 2020·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Kazutaka Sugimoto, David Y Chung
Jan 9, 2019·Frontiers in Neuroscience·Peter Van Dyken, Baptiste Lacoste
May 3, 2019·The Journal of Headache and Pain·Andrea M HarriottShih-Pin Chen
Jan 10, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Lei WeiJianjian Shi
Apr 4, 2020·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Karl SchoknechtJens P Dreier
Jul 13, 2019·Annual Review of Cell and Developmental Biology·Urs H LangenChenghua Gu
Jun 12, 2020·Frontiers in Cell and Developmental Biology·Irina FilchenkoLorenz Hirt
Jul 10, 2020·Stroke; a Journal of Cerebral Circulation·Kazutaka SugimotoCenk Ayata
Jun 25, 2019·Frontiers in Aging Neuroscience·Rubem Carlos Araújo Guedes, Ricardo Abadie-Guedes
Feb 11, 2020·Frontiers in Neuroscience·Marco TjakraGuixue Wang
Oct 29, 2020·The Journal of Headache and Pain·Kazutaka SugimotoCenk Ayata
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May 22, 2021·Neurology·Eric E SmithSteven M Greenberg
Aug 28, 2021·International Journal of Molecular Sciences·Gaku YamanakaHisashi Kawashima

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