Cilostazol preserves CA1 hippocampus and enhances generation of immature neuroblasts in dentate gyrus after transient forebrain ischemia in rats |
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Authors: | Lee Jeong Hyun Shin Hwa Kyoung Park So Youn Kim Chi Dae Lee Won Suk Hong Ki Whan |
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Affiliation: | a Department of Pharmacology, College of Medicine, Pusan National University, Busan, Republic of Korea b Medical Research Center for Ischemic Tissue Regeneration, Pusan National University, 10 Ami-Dong 1-Ga, Seo-Gu, Busan 602-739, Republic of Korea |
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Abstract: | In the present study, cerebral ischemia was induced by a 10 min transient bilateral common carotid artery occlusion in rats combined with arterial blood pressure lowering to 37-42 mm Hg during occlusion. When histologically evaluated at 7 and 28 days after the forebrain ischemia (DAI) by staining with cresyl violet and Fluoro-Jade, the hippocampal CA1 region was most prominently damaged. At 7 DAI, treatment with cilostazol (60 mg/kg/day, orally) significantly reduced the neuronal damage in the CA1 region. The number of surviving neurons, visualized by NeuN immunostaining, in the CA1 region significantly increased at 7 and 28 DAI in the cilostazol-treated groups. To elucidate whether cilostazol enhances hippocampal neurogenesis after ischemia, we planned a co-labeling study using 5-bromo-2′-deoxyuridine (BrdU), NeuN (a marker for mature neurons) and doublecortin (DCX) (a marker for immature migratory neuroblasts). Double immunofluorescence staining at 7 DAI showed that cilostazol significantly increased the immunoreactivities of both DCX and phosphorylated cAMP-response element-binding protein (CREB) in the dentate gyrus that was co-expressed with BrdU. These results suggest that cilostazol has dual beneficial effects preserving the CA1 hippocampal region and promoting the generation of immature migratory neuroblasts in the dentate gyrus by upregulation of CREB phosphorylation after transient forebrain ischemia. |
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Keywords: | BrdU, 5-bromo-2&prime -deoxyuridine DCX, doublecortin DG, dentate gyrus SGZ, subgranular zone CREB, cyclic AMP-response element-binding protein PBS, phosphate buffered saline DAI, day after ischemia |
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