Tight junctions in the blood–brain barrier promote edema formation and infarct size in stroke – Ambivalent effects of sealing proteins

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

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Tight junctions in the blood–brain barrier promote edema formation and infarct size in stroke – Ambivalent effects of sealing proteins. / Winkler, Lars; Blasig, Rosel; Breitkreuz-Korff, Olga; Berndt, Philipp; Dithmer, Sophie; Helms, Hans C.; Puchkov, Dmytro; Devraj, Kavi; Kaya, Mehmet; Qin, Zhihai; Liebner, Stefan; Wolburg, Hartwig; Andjelkovic, Anuska V.; Rex, Andre; Blasig, Ingolf E.; Haseloff, Reiner F.

In: Journal of Cerebral Blood Flow and Metabolism, Vol. 41, No. 1, 2021, p. 132-145.

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

Harvard

Winkler, L, Blasig, R, Breitkreuz-Korff, O, Berndt, P, Dithmer, S, Helms, HC, Puchkov, D, Devraj, K, Kaya, M, Qin, Z, Liebner, S, Wolburg, H, Andjelkovic, AV, Rex, A, Blasig, IE & Haseloff, RF 2021, 'Tight junctions in the blood–brain barrier promote edema formation and infarct size in stroke – Ambivalent effects of sealing proteins', Journal of Cerebral Blood Flow and Metabolism, vol. 41, no. 1, pp. 132-145. https://doi.org/10.1177/0271678X20904687

APA

Winkler, L., Blasig, R., Breitkreuz-Korff, O., Berndt, P., Dithmer, S., Helms, H. C., Puchkov, D., Devraj, K., Kaya, M., Qin, Z., Liebner, S., Wolburg, H., Andjelkovic, A. V., Rex, A., Blasig, I. E., & Haseloff, R. F. (2021). Tight junctions in the blood–brain barrier promote edema formation and infarct size in stroke – Ambivalent effects of sealing proteins. Journal of Cerebral Blood Flow and Metabolism, 41(1), 132-145. https://doi.org/10.1177/0271678X20904687

Vancouver

Winkler L, Blasig R, Breitkreuz-Korff O, Berndt P, Dithmer S, Helms HC et al. Tight junctions in the blood–brain barrier promote edema formation and infarct size in stroke – Ambivalent effects of sealing proteins. Journal of Cerebral Blood Flow and Metabolism. 2021;41(1):132-145. https://doi.org/10.1177/0271678X20904687

Author

Winkler, Lars ; Blasig, Rosel ; Breitkreuz-Korff, Olga ; Berndt, Philipp ; Dithmer, Sophie ; Helms, Hans C. ; Puchkov, Dmytro ; Devraj, Kavi ; Kaya, Mehmet ; Qin, Zhihai ; Liebner, Stefan ; Wolburg, Hartwig ; Andjelkovic, Anuska V. ; Rex, Andre ; Blasig, Ingolf E. ; Haseloff, Reiner F. / Tight junctions in the blood–brain barrier promote edema formation and infarct size in stroke – Ambivalent effects of sealing proteins. In: Journal of Cerebral Blood Flow and Metabolism. 2021 ; Vol. 41, No. 1. pp. 132-145.

Bibtex

@article{ffe0340f2af74222a05c3beaa25dc08a,
title = "Tight junctions in the blood–brain barrier promote edema formation and infarct size in stroke – Ambivalent effects of sealing proteins",
abstract = "The outcome of stroke is greatly influenced by the state of the blood–brain barrier (BBB). The BBB endothelium is sealed paracellularly by tight junction (TJ) proteins, i.e., claudins (Cldns) and the redox regulator occludin. Functions of Cldn3 and occludin at the BBB are largely unknown, particularly after stroke. We address the effects of Cldn3 deficiency and stress factors on the BBB and its TJs. Cldn3 tightened the BBB for small molecules and ions, limited endothelial endocytosis, strengthened the TJ structure and controlled Cldn1 expression. After middle cerebral artery occlusion (MCAO) and 3-h reperfusion or hypoxia of isolated brain capillaries, Cldn1, Cldn3 and occludin were downregulated. In Cldn3 knockout mice (C3KO), the reduction in Cldn1 was even greater and TJ ultrastructure was impaired; 48 h after MCAO of wt mice, infarct volumes were enlarged and edema developed, but endothelial TJs were preserved. In contrast, junctional localization of Cldn5 and occludin, TJ density, swelling and infarction size were reduced in affected brain areas of C3KO. Taken together, Cldn3 and occludin protect TJs in stroke, and this keeps the BBB intact. However, functional Cldn3, Cldn3-regulated TJ proteins and occludin promote edema and infarction, which suggests that TJ modulation could improve the outcome of stroke.",
keywords = "blood–brain barrier, claudins, occludin, Stroke, tight junctions",
author = "Lars Winkler and Rosel Blasig and Olga Breitkreuz-Korff and Philipp Berndt and Sophie Dithmer and Helms, {Hans C.} and Dmytro Puchkov and Kavi Devraj and Mehmet Kaya and Zhihai Qin and Stefan Liebner and Hartwig Wolburg and Andjelkovic, {Anuska V.} and Andre Rex and Blasig, {Ingolf E.} and Haseloff, {Reiner F.}",
year = "2021",
doi = "10.1177/0271678X20904687",
language = "English",
volume = "41",
pages = "132--145",
journal = "Journal of Cerebral Blood Flow and Metabolism",
issn = "0271-678X",
publisher = "SAGE Publications",
number = "1",

}

RIS

TY - JOUR

T1 - Tight junctions in the blood–brain barrier promote edema formation and infarct size in stroke – Ambivalent effects of sealing proteins

AU - Winkler, Lars

AU - Blasig, Rosel

AU - Breitkreuz-Korff, Olga

AU - Berndt, Philipp

AU - Dithmer, Sophie

AU - Helms, Hans C.

AU - Puchkov, Dmytro

AU - Devraj, Kavi

AU - Kaya, Mehmet

AU - Qin, Zhihai

AU - Liebner, Stefan

AU - Wolburg, Hartwig

AU - Andjelkovic, Anuska V.

AU - Rex, Andre

AU - Blasig, Ingolf E.

AU - Haseloff, Reiner F.

PY - 2021

Y1 - 2021

N2 - The outcome of stroke is greatly influenced by the state of the blood–brain barrier (BBB). The BBB endothelium is sealed paracellularly by tight junction (TJ) proteins, i.e., claudins (Cldns) and the redox regulator occludin. Functions of Cldn3 and occludin at the BBB are largely unknown, particularly after stroke. We address the effects of Cldn3 deficiency and stress factors on the BBB and its TJs. Cldn3 tightened the BBB for small molecules and ions, limited endothelial endocytosis, strengthened the TJ structure and controlled Cldn1 expression. After middle cerebral artery occlusion (MCAO) and 3-h reperfusion or hypoxia of isolated brain capillaries, Cldn1, Cldn3 and occludin were downregulated. In Cldn3 knockout mice (C3KO), the reduction in Cldn1 was even greater and TJ ultrastructure was impaired; 48 h after MCAO of wt mice, infarct volumes were enlarged and edema developed, but endothelial TJs were preserved. In contrast, junctional localization of Cldn5 and occludin, TJ density, swelling and infarction size were reduced in affected brain areas of C3KO. Taken together, Cldn3 and occludin protect TJs in stroke, and this keeps the BBB intact. However, functional Cldn3, Cldn3-regulated TJ proteins and occludin promote edema and infarction, which suggests that TJ modulation could improve the outcome of stroke.

AB - The outcome of stroke is greatly influenced by the state of the blood–brain barrier (BBB). The BBB endothelium is sealed paracellularly by tight junction (TJ) proteins, i.e., claudins (Cldns) and the redox regulator occludin. Functions of Cldn3 and occludin at the BBB are largely unknown, particularly after stroke. We address the effects of Cldn3 deficiency and stress factors on the BBB and its TJs. Cldn3 tightened the BBB for small molecules and ions, limited endothelial endocytosis, strengthened the TJ structure and controlled Cldn1 expression. After middle cerebral artery occlusion (MCAO) and 3-h reperfusion or hypoxia of isolated brain capillaries, Cldn1, Cldn3 and occludin were downregulated. In Cldn3 knockout mice (C3KO), the reduction in Cldn1 was even greater and TJ ultrastructure was impaired; 48 h after MCAO of wt mice, infarct volumes were enlarged and edema developed, but endothelial TJs were preserved. In contrast, junctional localization of Cldn5 and occludin, TJ density, swelling and infarction size were reduced in affected brain areas of C3KO. Taken together, Cldn3 and occludin protect TJs in stroke, and this keeps the BBB intact. However, functional Cldn3, Cldn3-regulated TJ proteins and occludin promote edema and infarction, which suggests that TJ modulation could improve the outcome of stroke.

KW - blood–brain barrier

KW - claudins

KW - occludin

KW - Stroke

KW - tight junctions

U2 - 10.1177/0271678X20904687

DO - 10.1177/0271678X20904687

M3 - Journal article

C2 - 32054373

AN - SCOPUS:85079368467

VL - 41

SP - 132

EP - 145

JO - Journal of Cerebral Blood Flow and Metabolism

JF - Journal of Cerebral Blood Flow and Metabolism

SN - 0271-678X

IS - 1

ER -

ID: 238694987