Desferrioxamine induces delayed tolerance against cerebral ischemia in vivo and in vitro
Desferrioxamine induces delayed tolerance against cerebral ischemia in vivo and in vitro
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DOI：
10.1097/00004647-200205000-00003
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发表时间：
2002-05-01
影响因子：
6.3
通讯作者：
Meisel, A
中科院分区：
文献类型：
--
作者：
Prass, K;Ruscher, K;Meisel, A
广泛处方的药物去铁胺是已知的低氧诱导转录因子I（HIF-1）和促红细胞生成素的后续转录的激活剂。在大脑里。HIF-1是缺氧转录反应的主开关，而促红细胞生成素是一种有效的神经保护剂。作者表明，去铁胺剂量依赖性和时间依赖性诱导耐受大鼠和小鼠的局灶性脑缺血，并对纯化的皮质神经元的氧-葡萄糖剥夺。去铁胺在体内诱导HIF-1 DNA结合和促红细胞生成素的转录，其时间动力学与耐受诱导一致。去铁胺是一种很有前途的药物，用于诱导人体缺血耐受。
The widely prescribed drug desferrioxamine is a known activator of the hypoxia-inducible transcription factor I (HIF-1) and the subsequent transcription of erythropoietin. In the brain. HIF-1 is a master switch of the transcriptional response to hypoxia, whereas erythropoietin is a potent neuroprotectant. The authors show that desferrioxamine dose-dependently and time-dependently induces tolerance against focal cerebral ischemia in rats and mice, and against oxygen-glucose deprivation in purified cortical neurons. Desferrioxamine induced HIF-1 DNA binding and transcription of erythropoietin in vivo, the temporal kinetics of which were congruent with tolerance induction. Desferrioxamine is a promising drug for the induction of tolerance in humans when ischemia can be anticipated.