title: Role of hydrogen sulfide in early blood-brain barrier disruption following transient focal cerebral ischemia.
abstract: We determined the role of endogenous hydrogen sulfide (H2S) in cerebral vasodilation/hyperemia and early BBB disruption following ischemic stroke. A cranial window was prepared over the left frontal, parietal and temporal cortex in mice. Transient focal cerebral Ischemia was induced by directly ligating the middle cerebral artery (MCA) for two hours. Regional vascular response and cerebral blood flow (CBF) during ischemia and reperfusion were measured in real time. Early BBB disruption was assessed by Evans Blue (EB) and sodium fluorescein (Na-F) extravasation at 3 hours of reperfusion. Topical treatment with DL-propargylglycine (PAG, an inhibitor for cystathionine γ-lyase (CSE)) and aspartate (ASP, inhibitor for cysteine aminotransferase/3-mercaptopyruvate sulfurtransferase (CAT/3-MST)), but not O-(Carboxymethyl)hydroxylamine hemihydrochloride (CHH, an inhibitor for cystathionine β-synthase (CBS)), abolished postischemic cerebral vasodilation/hyperemia and prevented EB and Na-F extravasation. CSE knockout (CSE-/-) reduced postischemic cerebral vasodilation/hyperemia but only inhibited Na-F extravasation. An upregulated CBS was found in cerebral cortex of CSE-/- mice. Topical treatment with CHH didn't further alter postischemic cerebral vasodilation/hyperemia, but prevented EB extravasation in CSE-/- mice. In addition, L-cysteine-induced hydrogen sulfide (H2S) production similarly increased in ischemic side cerebral cortex of control and CSE-/- mice. Our findings suggest that endogenous production of H2S by CSE and CAT/3-MST during reperfusion may be involved in postischemic cerebral vasodilation/hyperemia and play an important role in early BBB disruption following transient focal cerebral ischemia.
authors.affiliation: Department of Cellular Biology & Anatomy, Louisiana State University Health Sciences Center-Shreveport, Shreveport, Louisiana, United States of America.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: Department of Cellular Biology & Anatomy, Louisiana State University Health Sciences Center-Shreveport, Shreveport, Louisiana, United States of America.
authors.forename: Chun
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Cellular Biology & Anatomy, Louisiana State University Health Sciences Center-Shreveport, Shreveport, Louisiana, United States of America.
authors.forename: Morganne L
authors.initials: ML
authors.lastname: Manuel
authors.affiliation: Department of Cellular Biology & Anatomy, Louisiana State University Health Sciences Center-Shreveport, Shreveport, Louisiana, United States of America.
authors.forename: Shuai
authors.initials: S
authors.lastname: Yuan
authors.affiliation: Department of Pathology, Louisiana State University Health Sciences Center-Shreveport, Shreveport, Louisiana, United States of America.
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Kevil
authors.affiliation: Department of Cellular Biology & Anatomy, Louisiana State University Health Sciences Center-Shreveport, Shreveport, Louisiana, United States of America.
authors.forename: Kimberly D
authors.initials: KD
authors.lastname: McCarter
authors.affiliation: Department of Cellular Biology & Anatomy, Louisiana State University Health Sciences Center-Shreveport, Shreveport, Louisiana, United States of America.
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
authors.affiliation: Department of Cellular Biology & Anatomy, Louisiana State University Health Sciences Center-Shreveport, Shreveport, Louisiana, United States of America.
authors.forename: Hong
authors.initials: H
authors.lastname: Sun
mesh_terms: D000480:Alkynes / Q000494:pharmacology; D000818:Animals; D001224:Aspartic Acid / Q000494:pharmacology; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism*; D002540:Cerebral Cortex / Q000098:blood supply / Q000378:metabolism; D003541:Cystathionine beta-Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D003542:Cystathionine gamma-Lyase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D006862:Hydrogen Sulfide / Q000378:metabolism*; D002546:Ischemic Attack, Transient / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013466:Sulfurtransferases / Q000037:antagonists & inhibitors / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects
chemical_list: D000480:Alkynes; D001224:Aspartic Acid; C009055:propargylglycine; D013466:Sulfurtransferases; C021550:3-mercaptopyruvate sulphurtransferase; D003541:Cystathionine beta-Synthase; D003542:Cystathionine gamma-Lyase; D005998:Glycine; D006862:Hydrogen Sulfide