Hydrogen sulfide protects blood-brain barrier integrity following cerebral ischemia

Yali Wang, Jia Jia, Guizhen Ao, Lifang Hu, Hui Liu, Yunqi Xiao, Huaping Du, Nabil Alkayed, Chun Feng Liu, Jian Cheng

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

By using two structurally unrelated hydrogen sulfide (H2S) donors 5-(4-methoxyphenyl) -3H-1, 2-dithiole-3-thione (ADT) and sodium hydrosulfide (NaHS), this study investigated if H2S protected blood-brain barrier (BBB) integrity following middle cerebral artery occlusion (MCAO). ICR mice underwent MCAO and received H2S donors at 3 h after reperfusion. Infarction, neurological scores, brain edema, Evans blue (EB) extravasation, and tight junction protein expression were examined at 48 h after MCAO. We also investigated if ADT protected BBB integrity by suppressing post-ischemic inflammation-induced Matrix Metalloproteimase-9 (MMP9) and Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX). ADT increased blood H2S concentrations, decreased infarction, and improved neurological deficits. Particularly, ADT reduced EB extravasation, brain edema and preserved expression of tight junction proteins in the ischemic brain. NaHS also increased blood H2S levels and reduced EB extravasation following MCAO. Moreover, ADT inhibited expression of pro-inflammatory markers induced Nitric Oxide Synthase (iNOS) and IL-1β while enhanced expression of anti-inflammatory markers arginase 1 and IL-10 in the ischemic brain. Accordingly, ADT attenuated ischemia-induced expression and activity of MMP9. Moreover, ADT reduced NOX-4 mRNA expression, NOX activity, and inhibited nuclear translocation of Nuclear Factor Kappa-B (NF-κB) in the ischemic brain. In conclusion, H2S donors protected BBB integrity following experimental stroke possibly by acting through NF-κB inhibition to suppress neuroinflammation induction of MMP9 and NOX4-derived free radicals.

Original languageEnglish (US)
Pages (from-to)827-838
Number of pages12
JournalJournal of Neurochemistry
Volume129
Issue number5
DOIs
StatePublished - 2014

Fingerprint

Hydrogen Sulfide
Middle Cerebral Artery Infarction
Brain Ischemia
Blood-Brain Barrier
Evans Blue
Brain
Tight Junction Proteins
NF-kappa B
NADPH Oxidase
Brain Edema
Infarction
Anethole Trithione
Arginase
Blood
Inbred ICR Mouse
Interleukin-1
NADP
Nitric Oxide Synthase
Interleukin-10
Reperfusion

Keywords

  • Blood-brain barrier
  • cerebral ischemia
  • hydrogen sulfide
  • vasoprotection

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Wang, Y., Jia, J., Ao, G., Hu, L., Liu, H., Xiao, Y., ... Cheng, J. (2014). Hydrogen sulfide protects blood-brain barrier integrity following cerebral ischemia. Journal of Neurochemistry, 129(5), 827-838. https://doi.org/10.1111/jnc.12695

Hydrogen sulfide protects blood-brain barrier integrity following cerebral ischemia. / Wang, Yali; Jia, Jia; Ao, Guizhen; Hu, Lifang; Liu, Hui; Xiao, Yunqi; Du, Huaping; Alkayed, Nabil; Liu, Chun Feng; Cheng, Jian.

In: Journal of Neurochemistry, Vol. 129, No. 5, 2014, p. 827-838.

Research output: Contribution to journalArticle

Wang, Y, Jia, J, Ao, G, Hu, L, Liu, H, Xiao, Y, Du, H, Alkayed, N, Liu, CF & Cheng, J 2014, 'Hydrogen sulfide protects blood-brain barrier integrity following cerebral ischemia', Journal of Neurochemistry, vol. 129, no. 5, pp. 827-838. https://doi.org/10.1111/jnc.12695
Wang, Yali ; Jia, Jia ; Ao, Guizhen ; Hu, Lifang ; Liu, Hui ; Xiao, Yunqi ; Du, Huaping ; Alkayed, Nabil ; Liu, Chun Feng ; Cheng, Jian. / Hydrogen sulfide protects blood-brain barrier integrity following cerebral ischemia. In: Journal of Neurochemistry. 2014 ; Vol. 129, No. 5. pp. 827-838.
@article{2e162a58fdbe4f408fdc3b055980957a,
title = "Hydrogen sulfide protects blood-brain barrier integrity following cerebral ischemia",
abstract = "By using two structurally unrelated hydrogen sulfide (H2S) donors 5-(4-methoxyphenyl) -3H-1, 2-dithiole-3-thione (ADT) and sodium hydrosulfide (NaHS), this study investigated if H2S protected blood-brain barrier (BBB) integrity following middle cerebral artery occlusion (MCAO). ICR mice underwent MCAO and received H2S donors at 3 h after reperfusion. Infarction, neurological scores, brain edema, Evans blue (EB) extravasation, and tight junction protein expression were examined at 48 h after MCAO. We also investigated if ADT protected BBB integrity by suppressing post-ischemic inflammation-induced Matrix Metalloproteimase-9 (MMP9) and Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX). ADT increased blood H2S concentrations, decreased infarction, and improved neurological deficits. Particularly, ADT reduced EB extravasation, brain edema and preserved expression of tight junction proteins in the ischemic brain. NaHS also increased blood H2S levels and reduced EB extravasation following MCAO. Moreover, ADT inhibited expression of pro-inflammatory markers induced Nitric Oxide Synthase (iNOS) and IL-1β while enhanced expression of anti-inflammatory markers arginase 1 and IL-10 in the ischemic brain. Accordingly, ADT attenuated ischemia-induced expression and activity of MMP9. Moreover, ADT reduced NOX-4 mRNA expression, NOX activity, and inhibited nuclear translocation of Nuclear Factor Kappa-B (NF-κB) in the ischemic brain. In conclusion, H2S donors protected BBB integrity following experimental stroke possibly by acting through NF-κB inhibition to suppress neuroinflammation induction of MMP9 and NOX4-derived free radicals.",
keywords = "Blood-brain barrier, cerebral ischemia, hydrogen sulfide, vasoprotection",
author = "Yali Wang and Jia Jia and Guizhen Ao and Lifang Hu and Hui Liu and Yunqi Xiao and Huaping Du and Nabil Alkayed and Liu, {Chun Feng} and Jian Cheng",
year = "2014",
doi = "10.1111/jnc.12695",
language = "English (US)",
volume = "129",
pages = "827--838",
journal = "Journal of Neurochemistry",
issn = "0022-3042",
publisher = "Wiley-Blackwell",
number = "5",

}

TY - JOUR

T1 - Hydrogen sulfide protects blood-brain barrier integrity following cerebral ischemia

AU - Wang, Yali

AU - Jia, Jia

AU - Ao, Guizhen

AU - Hu, Lifang

AU - Liu, Hui

AU - Xiao, Yunqi

AU - Du, Huaping

AU - Alkayed, Nabil

AU - Liu, Chun Feng

AU - Cheng, Jian

PY - 2014

Y1 - 2014

N2 - By using two structurally unrelated hydrogen sulfide (H2S) donors 5-(4-methoxyphenyl) -3H-1, 2-dithiole-3-thione (ADT) and sodium hydrosulfide (NaHS), this study investigated if H2S protected blood-brain barrier (BBB) integrity following middle cerebral artery occlusion (MCAO). ICR mice underwent MCAO and received H2S donors at 3 h after reperfusion. Infarction, neurological scores, brain edema, Evans blue (EB) extravasation, and tight junction protein expression were examined at 48 h after MCAO. We also investigated if ADT protected BBB integrity by suppressing post-ischemic inflammation-induced Matrix Metalloproteimase-9 (MMP9) and Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX). ADT increased blood H2S concentrations, decreased infarction, and improved neurological deficits. Particularly, ADT reduced EB extravasation, brain edema and preserved expression of tight junction proteins in the ischemic brain. NaHS also increased blood H2S levels and reduced EB extravasation following MCAO. Moreover, ADT inhibited expression of pro-inflammatory markers induced Nitric Oxide Synthase (iNOS) and IL-1β while enhanced expression of anti-inflammatory markers arginase 1 and IL-10 in the ischemic brain. Accordingly, ADT attenuated ischemia-induced expression and activity of MMP9. Moreover, ADT reduced NOX-4 mRNA expression, NOX activity, and inhibited nuclear translocation of Nuclear Factor Kappa-B (NF-κB) in the ischemic brain. In conclusion, H2S donors protected BBB integrity following experimental stroke possibly by acting through NF-κB inhibition to suppress neuroinflammation induction of MMP9 and NOX4-derived free radicals.

AB - By using two structurally unrelated hydrogen sulfide (H2S) donors 5-(4-methoxyphenyl) -3H-1, 2-dithiole-3-thione (ADT) and sodium hydrosulfide (NaHS), this study investigated if H2S protected blood-brain barrier (BBB) integrity following middle cerebral artery occlusion (MCAO). ICR mice underwent MCAO and received H2S donors at 3 h after reperfusion. Infarction, neurological scores, brain edema, Evans blue (EB) extravasation, and tight junction protein expression were examined at 48 h after MCAO. We also investigated if ADT protected BBB integrity by suppressing post-ischemic inflammation-induced Matrix Metalloproteimase-9 (MMP9) and Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX). ADT increased blood H2S concentrations, decreased infarction, and improved neurological deficits. Particularly, ADT reduced EB extravasation, brain edema and preserved expression of tight junction proteins in the ischemic brain. NaHS also increased blood H2S levels and reduced EB extravasation following MCAO. Moreover, ADT inhibited expression of pro-inflammatory markers induced Nitric Oxide Synthase (iNOS) and IL-1β while enhanced expression of anti-inflammatory markers arginase 1 and IL-10 in the ischemic brain. Accordingly, ADT attenuated ischemia-induced expression and activity of MMP9. Moreover, ADT reduced NOX-4 mRNA expression, NOX activity, and inhibited nuclear translocation of Nuclear Factor Kappa-B (NF-κB) in the ischemic brain. In conclusion, H2S donors protected BBB integrity following experimental stroke possibly by acting through NF-κB inhibition to suppress neuroinflammation induction of MMP9 and NOX4-derived free radicals.

KW - Blood-brain barrier

KW - cerebral ischemia

KW - hydrogen sulfide

KW - vasoprotection

UR - http://www.scopus.com/inward/record.url?scp=84901193671&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84901193671&partnerID=8YFLogxK

U2 - 10.1111/jnc.12695

DO - 10.1111/jnc.12695

M3 - Article

VL - 129

SP - 827

EP - 838

JO - Journal of Neurochemistry

JF - Journal of Neurochemistry

SN - 0022-3042

IS - 5

ER -