Neuroprotective Potential of a Novel Soluble Guanylate Cyclase Stimulator the Riociguat Alone or in a Combination Manner With Resveratrol in Experimental Stroke Model in Rats

Abstract

In this study we aimed to examine the effect of novel vasodilatory drug Riociguat co-administration along resveratrol to recover neurodegeneration in experimental stroke injury. For that purpose, thirty-five adult female rats were divided into groups five (Control, MCAO, MCAO + R, MCAO + BAY, MCAO + C) of seven animals in each. Animals in Control group did not expose to any application during the experiment and sacrificed at the end of the study. Rats in the rest groups exposed to middle cerebral artery occlusionO) (MCAinduced ischemic stroke. MCAO + R group received 30 mg/kg resveratrol, and MCAO + BAY group received 10 mg/kg Riociguat. The MCAO + C group received both drugs simultaneously. The drugs were administered just before the reperfusion, and the additional e doses weradministered 24h, and 48h hours of reperfusion. All animals in this study were sacrificed at the 72nd hour of experiment. Total brainsreceived were for analysis. Results of this experiment indicated that MCAO led to severe injury in cerebral structure. Bax, IL-6 and IL-1 ss levelstissue were upregulated, but anti-apoptotic Bcl-2 immunoexpression was suppressed (p<0.05). In resveratrol and Riociguat treated animals, the neurodegenerations and apoptosis and inflammation associated protein expressions were improved compared to MCAO group, mosbut the success was obtained in combined treatment exposed animals in MCAO + C group. This study indicated that the novel solubleate guany cyclase stimulator Riociguat is not only a potent neuroprotective drug in MCAO induced stroke, but also synergistic administratio of Riociguat along with resveratrol have potential to increase the neuroprotective effect of resveratrol in experimental cerebral strokeosed rats.