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- W1569872036 abstract "Hydrogen sulfide (H2S) is a gaseous mediator with vasodilator and antioxidant properties produced by cystathionine γ-lyase (CSE) and cystathionine β-synthase (CBS). In the brain, CSE and CBS are predominant H2S-producing enzymes in vessels and astrocytes, respectively. We investigated cytoprotective properties of H2S in a model of cerebrovascular disease caused by neonatal seizures. In newborn piglets, bicuculline-induced epileptic seizures produce long-term cerebral vascular dysfunction. During seizures, brain CBS activity is increased as indicated by H2S elevation in periarachnoid cerebrospinal fluid (CSF) that was selectively inhibited by aminooxyacetate. We addressed the hypothesis that H2S improves the cerebral vascular outcome of seizures. An H2S donor NaHS (3 mg/kg) administered enterally or parenterally rapidly increased H2S in CSF. At this dose, NaHS had no effects on core body temperature, mean arterial blood pressure, or heart rate. To test the cytoprotective effects of NaHS, the drug was administered before or during seizures. Cerebral vascular reactivity to physiologically relevant vasodilators was tested by the cranial window technique 48 h after seizures. In the control group, we observed a great reduction in postictal dilator responses to endothelium- and/or astrocyte-dependent stimuli bradykinin, glutamate, and hemin. NaHS administered enterally or parenterally before or during seizures improved all postictal vascular responses. We conclude that H2S, endogenously produced in the brain via CBS activation during seizures, or pharmacologically delivered to the brain during a therapeutic window, reduces the adverse cerebral vascular outcome of neonatal seizures thus leading to vascular neuroprotection. The study was supported by NIH/NLBI." @default.
- W1569872036 created "2016-06-24" @default.
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- W1569872036 date "2015-04-01" @default.
- W1569872036 modified "2023-09-27" @default.
- W1569872036 title "Hydrogen Sulfide Is An Endogenous Cytoprotective Gaseous Mediator in Cerebral Circulation" @default.
- W1569872036 doi "https://doi.org/10.1096/fasebj.29.1_supplement.645.4" @default.
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