Neuroscience research
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Neuroscience research · Dec 2007
Edaravone inhibits the expression of vascular endothelial growth factor in human astrocytes exposed to hypoxia.
Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one), a free radical scavenger, reduces brain edema in patients with acute ischemic stroke. We have addressed the effect of edaravone on the expression of vascular endothelial growth factor (VEGF), a potential mediator of brain edema, in astrocytes exposed to hypoxia. Normal human astrocytes in culture were treated with edaravone, and the levels of VEGF mRNA and protein were analyzed by reverse transcription-polymerase chain reaction (RT-PCR), real-time quantitative PCR and enzyme-linked immunosorbent assay (ELISA). ⋯ ChIP assay confirmed that edaravone reduced HIF-1alpha binding to VEGF promoter. We conclude that edaravone inhibits VEGF expression in astrocytes exposed to hypoxia, at least partly, through the down-regulation of HIF-1alpha. These findings offer a partial explanation for the protective effect of edaravone on the development of brain edema in patients with acute ischemic stroke.
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Neuroscience research · Dec 2007
Adenosine induces expression of glial cell line-derived neurotrophic factor (GDNF) in primary rat astrocytes.
Adenosine, which accumulates rapidly during ischemia due to the breakdown of ATP, has beneficial effects in many tissues. We examined whether adenosine induces the production of glial cell line-derived neurotrophic factor (GDNF) in cultured astrocytes. We evaluated GDNF mRNA expression and GDNF production in astrocytes cultured with adenosine and the adenosine selective receptor agonists 5-(N-ethylcarboxamido) adenosine (NECA), N(6)-cyclopentyladenosine (CPA) and 2-p-(2-carboxyethyl) phenethylamino-5'-N-ethylcarboxamindo-adenosine hydrochloride (CGS 21680). ⋯ Furthermore, the amounts of GDNF produced were significantly reduced in astrocytes of the adenosine-treated SHRSP compared with those of WKY. These results indicate that adenosine induces the expression of GDNF, and adenosine A(2B) receptors participate in the regulation of GDNF levels in astrocytes. This expression was attenuated in astrocytes of SHRSP compared with those of WKY.