Normobaric hypoxia induces tolerance to focal permanent cerebral ischemia in association with an increased expression of hypoxia-inducible factor-1 and its target genes, erythropoietin and VEGF, in the adult mouse brain
Normobaric hypoxia induces tolerance to focal permanent cerebral ischemia in association with an increased expression of hypoxia-inducible factor-1 and its target genes, erythropoietin and VEGF, in the adult mouse brain
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DOI：
10.1097/00004647-200204000-00003
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发表时间：
2002-04-01
影响因子：
6.3
通讯作者：
Schumann-Bard, P
中科院分区：
文献类型：
--
作者：
Bernaudin, M;Nedelec, AS;Schumann-Bard, P
对脑缺血的耐受性是通过预处理亚致死性应激（例如缺血或缺氧）来实现的，其中Oi可用性的降低可能构成诱导耐受性的早期信号。根据这一概念，本研究表明，缺氧诱导耐受局灶性永久性缺血在成年小鼠。在缺血前24小时进行常压缺氧（8%O-2，持续1小时、3小时或6小时），与对照组相比，梗死体积减少约30%。为了阐明这种神经保护的机制，作者研究了预处理对脑缺氧诱导因子-1 α（HIF-1 α）及其靶基因促红细胞生成素和血管内皮生长因子（VEGF）表达的影响。缺氧，无论其持续时间（1小时，3小时，6小时），迅速增加HIF-1 α的核含量以及促红细胞生成素和VEGF的mRNA水平。此外，促红细胞生成素和VEGF在缺氧6小时后24小时在蛋白质水平上上调。作者的研究结果表明：（1）缺氧引起延迟性、短暂性（
Tolerance to cerebral ischemia is achieved by preconditioning sublethal stresses, such as ischemia or hypoxia, paradigms in which the decrease of 0, availability may constitute an early signal inducing tolerance. In accordance with this concept, this study shows that hypoxia induces tolerance against focal permanent ischemia in adult mice. Normobaric hypoxia (8% O-2 of 1-hour, 3-hour, or 6-hour duration), performed 24 hours before ischemia, reduces infarct volume by approximately 30% when compared with controls. To elucidate the mechanisms underlying this neuroprotection, the authors investigated the effects of preconditioning on cerebral expression of hypoxia-inducible factor-1alpha (HIF-1alpha) and its target genes, erythropoietin and vascular endothelial growth factor (VEGF). Hypoxia, whatever its duration (1 hour, 3 hours, 6 hours), rapidly increases the nuclear content of HIF-1alpha as well as the mRNA levels of erythropoietin and VEGF. Furthermore, erythropoietin and VEGF are upregulated at the protein level 24 hours after 6 hours of hypoxia. The authors' findings show that (1) hypoxia elicits a delayed, short-lasting (