Hydrogen Sulfide Is a Mediator of Cerebral Ischemic Damage
- 1 March 2006
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Stroke
- Vol. 37 (3), 889-893
- https://doi.org/10.1161/01.str.0000204184.34946.41
Abstract
Background and Purpose— We observed recently that elevated plasma cysteine levels are associated with poor clinical outcome in acute stroke patients. In a rat stroke model, cysteine administration increased the infarct volume apparently via its conversion to hydrogen sulfide (H 2 S). We therefore investigated the effects of H 2 S and the inhibition of its formation on stroke. Methods— Cerebral ischemia was studied in a rat stroke model created by permanent occlusion of the middle cerebral artery (MCAO). The resultant infarct volume was measured 24 hours after occlusion. Results— Administration of sodium hydrosulfide (NaHS, an H 2 S donor) significantly increased the infarct volume after MCAO. The NaHS-induced increase in infarct volume was abolished by the administration of dizolcilpine maleate (an N -methyl- d -aspartate receptor channel blocker). MCAO caused an increase in H 2 S level in the lesioned cortex as well as an increase in the H 2 S synthesizing activity. Administration of 4 different inhibitors of H 2 S synthesis reduced MCAO-induced infarct volume dose dependently. The potency of these inhibitors in effecting neuroprotection in vivo appeared to parallel their potency as inhibitors of H 2 S synthesis in vitro. It also appeared that most of the H 2 S synthesizing activity in the cortex results from the action of cystathionine β-synthase. Conclusions— The present results strongly suggest that H 2 S plays a part in cerebral ischemic damage after stroke. Inhibition of H 2 S synthesis should be investigated for its potential as a novel neuroprotective stroke therapy.Keywords
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