title: Neuroprotective effect of cilostazol against focal cerebral ischemia via antiapoptotic action in rats.
abstract: This study examined the protective effects of cilostazol on cerebral infarcts produced by subjecting rats to 2-h occlusion of the left middle cerebral artery followed by 24-h reperfusion. The ischemic cerebral infarct consistently involved the cortex and striatum. The infarct size was significantly reduced, when rats received 10 mg/kg cilostazol intravenously 5 min or 1 h after the completion of 2-h ischemia. Cyclic AMP level was significantly elevated in the cortex of 4- and 12-h reperfusion (P < 0.01) following treatment with cilostazol (10 mg/kg, 5 min after 2-h ischemia) accompanied by decreased tumor necrosis factor-alpha level. Samples from the regions corresponding to the penumbra showed markedly reduced Bcl-2 protein level and, in contrast, high levels of Bax protein and cytochrome c release. Cilostazol decreased Bax protein and cytochrome c release and increased the levels of Bcl-2 protein. Cilostazol (10(-7)-10(-5) M) potently and concentration dependently scavenged hydroxyl and peroxyl radicals. In conclusion, cilostazol treatment decreases ischemic brain infarction in association with inhibition of apoptotic and oxidative cell death.
authors.affiliation: Department of Pharmacology, College of Medicine, and Research Institute of Genetic Engineering, Pusan National University, Pusan, Korea.
authors.forename: Jae Moon
authors.initials: JM
authors.lastname: Choi
authors.forename: Hwa Kyoung
authors.initials: HK
authors.lastname: Shin
authors.forename: Ki Young
authors.initials: KY
authors.lastname: Kim
authors.forename: Jeong Hyun
authors.initials: JH
authors.lastname: Lee
authors.forename: Ki Whan
authors.initials: KW
authors.lastname: Hong
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D020520:Brain Infarction / Q000473:pathology / Q000517:prevention & control; D000077407:Cilostazol; D000242:Cyclic AMP / Q000378:metabolism; D003574:Cytochrome c Group / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D016166:Free Radical Scavengers / Q000378:metabolism; D019254:Genes, bcl-2; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000473:pathology / Q000517:prevention & control; D013777:Tetrazoles / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D051028:bcl-2-Associated X Protein
chemical_list: C494828:Bax protein, rat; D003574:Cytochrome c Group; D016166:Free Radical Scavengers; D018696:Neuroprotective Agents; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D013777:Tetrazoles; D014409:Tumor Necrosis Factor-alpha; D051028:bcl-2-Associated X Protein; D000242:Cyclic AMP; D000077407:Cilostazol