Abstract T P226: Cilostazol Can Attenuate Oxidative Stress by Suppressing Nox2 on Neurons in Mice Permanent Focal Ischemia
It has been reported that phosphodiesterase (PDE) 3 inhibitor cilostazol, which is used as an antiplatelet drug, could ameliorate ischemic brain injury. We aimed to investigate how cilostazol affected permanent focal ischemia. Male Balb/c mice were subjected to permanent middle cerebral artery occlusion. They were treated with cilostazol (10- mg/kg or 20-mg/kg) or vehicle 30 min and 24 h post-ischemia, and the infarct volume was assessed 48 h post-ischemia. The animals treated with 20-mg/kg cilostazol or vehicle were sacrificed 6 h or 24 h post-ischemia, and then the immunohistochemistry was performed to the brain sections. We demonstrated that the treatment with 20- mg/kg cilostazol significantly reduced infarct volume (70.1% vs. vehicle group). Immunohistochemistry against 8-hydroxydeoxyguanosine (OHdG) showed that some neurons suffered from oxidative stress in peri-infarct 6 h post-ischemia. The treatment with cilostazol reduced the number of 8-OHdG-positive neurons significantly (65.8 ± 33.5% in vehicle group and 21.3 ± 9.9% in cilostazol group). Moreover, the number of NADPH oxidase (NOX) 2-positive neurons was also reduced significantly (57.0 ± 13.6% in vehicle group and 26.5 ± 16.7% in cilostazol group). On the other hand, immunohistochemistry against phosphorylated cyclic-AMP response element binding protein (pCREB) showed that the number of the pCREB-positive neurons in peri-infarct of the cilostazol-treated animals was significantly higher than in vehicle-treated ones 24 h post-ischemia. These findings suggested that cilostazol could have multi-mechanisms to ameliorate the tissue damage, one was to attenuate oxidative stress by suppressing NOX2 on ischemic neurons, and another was anti-apoptotic effect through the pathway of Akt/pCREB.
Author Disclosures: H. Shichinohe: None. S. Kuroda: None. C. Tan: None. T. Abumiya: None. N. Nakayama: None. K. Kazumata: None. M. Hokari: None. K. Houkin: None.
- © 2015 by American Heart Association, Inc.