Hydrogen Sulfide Attenuates Neuronal Injury Induced by Vascular Dementia Via Inhibiting Apoptosis in Rats

Abstract

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.

Hydrogen sulfide improves neural function in rats following cardiopulmonary resuscitation

“…This may be attributable to the hypothesis that a lower concentration of H 2 S exerts a protective effect on cells while higher levels of H 2 S exposure lead to cytotoxicity (41). In the present study, 14 µmol/kg/day NaHS was intraperitoneally administered, and it has previously been confirmed that the protective effect against neuronal injury conferred by NaHS is dose-dependent (42). In addition to its function as an inhibitor of CBS, hydroxylamine can be metabolized to NO (43), which may be neurotoxic and contributes to neuronal damage (44).…”

Sodium hydrosulfide alleviates lung inflammation and cell apoptosis following resuscitated hemorrhagic shock in rats

“…Niu and colleagues reported that neutralization of FasL attenuates brain inflammation in a model of experimental stroke in mice [41] . The anti-apoptotic effects of H 2 S have been widely reported by researchers both in vivo and in vitro [42][43][44] . However, few studies have investigated the effects of H 2 S on HS, and even fewer have addressed the underlying mechanisms.…”

Brain, Learning, and Memory: Role of H2S in Neurodegenerative Diseases

“…The antiapoptotic effect was supported by other studies as well. Zhang et al found out that H 2 S attenuated neuronal injury induced by vascular dementia via inhibiting apoptosis in rats (Zhang et al 2009). In yet another study, H 2 S imparted the cytoprotective effect to PC12 cells against amyloid β (25-35)-induced apoptosis (Tang et al 2008).…”