The Neuroprotective Effect of Caffeic Acid Phenethyl Ester on Global Ischemia-Reperfusion Injury in Rat Brains

The aim of this study was to investigate the neuroprotective effects of caffeic acid phenethyl ester (CAPE) on phosphodiesterase 4 (PDE4) mRNA isoenzymes, oxidant and antioxidant defence in ischemia/reperfusion (I/R) injured rat brains. Twenty-one rats were randomly divided into three equal groups: sham-control, ischemia/reperfusion (I/R) and I/R+CAPE. Rats in sham-control group underwent only surgical intervention without bilateral common carotid artery occlusion. Ischemia/reperfusion was induced by bilateral common carotid artery occlusion with atraumatic clips for 30 min, followed by artery reopening. The I/R+CAPE group was subjected to the same surgical procedure as I/R group, but CAPE was administered intraperitoneally at the dose of 15 mu mol kg(-1) twice, 1 h before occlusion and at 12th h of reperfusion. The rats were sacrificed 24 h after I/R. The cAMP concentration was analyzed by ELISA and PDE4 isozyme mRNA transcriptions were evaluated by qRT-PCR methodology in the brain cortex. Ischemia-induced NO production was significantly attenuated by CAPE in the cerebral cortex. CAPE significantly enhanced GSH-Px activity, while SOD, CAT and XO activities non-significantly changed, as compared to the I/R group. CAPE significantly decreased PDE4A and PDE4B transcripts, without changing cAMP levels compared to I/R group. Ischemia-induced neurologic deficit scores were reduced by CAPE. These results suggest that CAPE slightly modulates the antioxidant defense system and NO release in rat brain during global cerebral ischemia/reperfusion injury. In addition, CAPE treatments produce the neuroprotective effect by reducing the levels of some PDE4 transcriptions.