Hydrogen sulfide attenuates neuronal injury induced by vascular dementia via inhibiting apoptosis in rats.

Hydrogen sulfide (H(2)S) is a gaseous messenger and serves as an important neuromodulator in the central nervous system. The current study was undertaken to investigate whether H(2)S attenuates the neuronal injury induced by vascular dementia (VD). Rats were subjected to bilateral common carotid artery and vertebral artery occlusion for 5 min three times in an interval of 5 min to induce VD. An H(2)S donor, sodium hydrosulfide (NaHS) or an inhibitor of cystathionine-beta-synthase, hydroxylamine (HA) was administered intraperitoneally. The number of neurons in the hippocampus was determined by hematoxylin and eosin staining, and the performance of learning and memory was tested by the Morris water maze. H(2)S content in plasma was evaluated. Apoptosis in the hippocampus was assessed by flow cytometry. In addition, Bcl-2 and Bax expression was analyzed by immunohistochemical staining. The neuronal injury occurred gradually with a decreased number of neurons and increased apoptosis ratio in the hippocampus over 720 h after VD. The H(2)S level was also gradually decreased in plasma over 720 h after VD, which negatively correlated with the apoptosis ratio in the hippocampus after VD. In addition, NaHS treatment significantly attenuated neuronal injury and improved neural functional performance, whereas HA exaggerated the neuronal injury and exacerbated learning and memory at 720 h after VD. Furthermore, NaHS treatment markedly improved the ratio of Bcl-2 over Bax with increased Bcl-2 expression and decreased Bax expression. In contrast, HA reduced the ratio of Bcl-2 over Bax. It is suggested that H(2)S attenuates VD injury via inhibiting apoptosis and may have potential therapeutic value for VD.