Abstract
The aim of this study was to observe the expression of poly ADP-ribose polymerase (PARP) and apoptosis-inducing factor (AIF) in the CA1 region of the hippocampus and to explore whether cilostazol pretreatment exerts a protective effect on the brain through the PARP/AIF-mediated pathway in a rat model of cerebral ischemia-reperfusion. Rats were randomly divided into three groups: Sham-surgery, ischemia-reperfusion and cilostazol (n=45 rats/group). Rat models of middle cerebral artery occlusion were prepared using a thread occlusion method. Rats in the cilostazol group were administered 30 mg/kg intragastric cilostazol 6 and 2 h before brain ischemia, respectively. Following reperfusion, samples were collected at different time-points (6, 24 and 72 h) and each group was further subdivided into three subgroups (n=15 rats/subgroup). Apoptosis was measured using the terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling method. The protein expression levels of AIF and PARP were detected using western blot analysis and the expression levels of AIF mRNA were determined using the reverse transcription-polymerase chain reaction. AIF nuclear translocation occurred following local cerebral ischemia-reperfusion injury. Apoptosis, levels of AIF and PARP protein expression and levels of AIF mRNA expression were significantly increased in the ischemia-reperfusion group compared with the sham-surgery group (P<0.05). However, apoptosis and the expression levels of AIF protein, PARP protein and AIF mRNA at different time-points were significantly decreased in the cilostazol group compared with the ischemia-reperfusion group (P<0.05). In conclusion, cilostazol has a protective effect on rat cerebral ischemia-reperfusion injury, and acts by inhibiting nerve cell apoptosis by preventing the excessive activation of PARP and AIF nuclear translocation.
Highlights
Cilostazol, a selective inhibitor of phosphodiesterase III, is able to inhibit PDE-3 activity with the increase in intracellular cyclic adenosine monophosphate (cAMP) concentration which regulates cell function, inhibits platelet aggregation, prevents thrombosis, relaxes vascular smooth muscle, inhibits cell proliferation and regulates blood lipid level
Compared with the ischemia‐reperfusion group, the apoptosis rate was significantly decreased in the cilostazol group at all time‐points (P
Cilostazol is a selective inhibitor of the cyclic nucleotide PDE‐3 and increases cyclic adenosine monophosphate levels in platelets and vascular endothelial cells by inhibiting PDE‐3 activity and cAMP degradation
Summary
Cilostazol, a selective inhibitor of phosphodiesterase III, is able to inhibit PDE-3 activity with the increase in intracellular cAMP concentration which regulates cell function, inhibits platelet aggregation, prevents thrombosis, relaxes vascular smooth muscle, inhibits cell proliferation and regulates blood lipid level. Apoptosis-inducing factor (AIF) is associated with nerve cell death. The excessive activation of poly ADP-ribose polymerase (PARP) sends the nuclear signal to the mitochondrion, triggering AIF release from the mitochondrion to the cell nucleus with chromatin condensation and DNA fragments. Cilostazol has protective effects on cerebral ischemia-reperfusion injury and the protective effects are associated with PARP inhibition [1]. Non‐caspase‐mediated apoptotic pathways exist, including the poly ADP‐ribose polymerase (PARP)/apoptosis‐inducing factor (AIF)‐mediated apoptotic pathway [2-4]. The PARP/AIF‐mediated apoptotic pathway is an important pathway that is present in numerous eukaryotic organisms. The effects of cilostazol on the PARP/AIF‐mediated apoptotic pathway in a rat model of cerebral ischemia‐reperfusion injury were investigated, providing an experimental basis for the prevention and treatment of cerebrovascular disease
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
