SAM, a cystathionine beta-synthase activator, promotes hydrogen sulfide to promote neural repair resulting from massive cerebral infarction induced by middle cerebral artery occlusion.

Abstract

Neurologic deterioration after massive cerebral infarct should be identified at an early stage for medical and surgical treatments. We investigated the effect of hydrogen sulfide on the excitotoxity of PC12 cells exposed to oxygen-glucose deprivation (OGD) and its effect on the apoptosis of brain tissues in rats with middle cerebral artery occlusion (MCAO). Rats with MCAO were treated with SAM, a cystathionine beta-synthase (CBS) activator, or AOAA, a CBS inhibitor. Hydrogen sulfide content in the brain tissues of infarcted patients or rats with MCAO was decreased, whereas glutamate (GLU) content was increased. In addition, SAM reduced reactive oxygen species content, lactate dehydrogenase release, and apoptosis levels in the brain tissues of rats with MCAO. The PC12 cells that were exposed to OGD were also treated with 20mM GLU and later treated with SAM or AOAA. In PC12 cells, SAM reduced the apoptosis caused by GLU after OGD. The protective effects of hydrogen sulfide was elicited through the sulfur-sulfhydrylation modification of NMDAR and the induction of ERK/MAPK signaling. Our results showed that hydrogen sulfide exerts a protective effect on the PC12 cells and the rats with MCAO, which might represent a possible therapeutic agent against massive cerebral infarct.