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Vol. 300, Issue 3, 787-793, March 2002
Department of Pharmacology, College of Medicine, and Research
Institute of Genetic Engineering, Pusan National University, Pusan,
Korea
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-
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.
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