Hydrogen sulfide protects blood–brain barrier integrity following cerebral ischemia. (27th March 2014)

• Record Type: Journal Article
• Authors: Wang, Yali; Jia, Jia; Ao, Guizhen; Hu, Lifang; Liu, Hui; Xiao, Yunqi; Du, Huaping; Alkayed, Nabil J.; Liu, Chun‐Feng; Cheng, Jian
• Is Part Of: Journal of neurochemistry. Volume 129:Number 5(2014:Jun.)
• Page Start: 827
• Page End: 838
• Publication Date: 2014-03-27
• Subjects: Neurochemistry -- Periodicals; 616.8042
• DOI: 10.1111/jnc.12695
• Languages: English
• ISSNs: 0022-3042

Abstract

<abstract abstract-type="main" id="jnc12695-abs-0001"> <title>Abstract</title> <p>By using two structurally unrelated hydrogen sulfide (H<sub>2</sub>S) donors 5‐(4‐methoxyphenyl) ‐3H‐1, 2‐dithiole‐3‐thione (ADT) and sodium hydrosulfide (NaHS), this study investigated if H<sub>2</sub>S protected blood–brain barrier (BBB) integrity following middle cerebral artery occlusion (MCAO). ICR mice underwent MCAO and received H<sub>2</sub>S 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 H<sub>2</sub>S 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 H<sub>2</sub>S 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, H<sub>2</sub>S 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. <boxed-text content-type="graphic" id="jnc12695-blkfxd-0001" position="anchor" orientation="portrait"><graphic position="anchor" mimetype="image" xlink:href="ark:/27927/pgh5j0p2x0" orientation="portrait" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /></boxed-text></p> <p>To determine H<sub>2</sub>S effects on blood–brain barrier (BBB) disruption following stroke, we used two structurally unrelated H<sub>2</sub>S donors ADT and NaHS. Both ADT and NaHS remarkably protected BBB integrity following experimental stroke. The slow‐releasing donor ADT also reduced post‐ischemic inflammation‐induced expression and activity of MMP9 and NOX4 in the ischemic brain possibly by inhibiting NF‐κB activation.</p> </abstract>