Hypoxia-inducible factor 1 is essential for spontaneous recovery from traumatic brain injury and is a key mediator of heat acclimation induced neuroprotection
Hypoxia-inducible factor 1 is essential for spontaneous recovery from traumatic brain injury and is a key mediator of heat acclimation induced neuroprotection
复制标题
DOI：
10.1038/jcbfm.2012.193
复制
发表时间：
2013-04-01
影响因子：
6.3
通讯作者：
Shohami, Esther
中科院分区：
文献类型：
--
作者：
Umschweif, Gali;Alexandrovich, Alexander G.;Shohami, Esther
热适应（HA）是一种成熟的预适应模型，在啮齿动物创伤性脑损伤（TBI）模型中赋予神经保护作用。它增加了神经保护因子，其中之一是缺氧诱导因子1 α（HIF-1 α），它在对损伤后缺血的反应中很重要。然而，关于HIF-1a在TBI中的作用及其对HA保护表型的建立的贡献知之甚少。因此，我们的目的是探讨HIF-1 α在TBI防御机制以及HA诱导的神经保护中的作用。在损伤的正常体温（NT）或HA小鼠中，使用吖啶黄抑制HIF-1。TBI后，我们评估了运动功能恢复、病变体积、水肿形成和体温以及HIF-1下游转录靶点，如葡萄糖转运蛋白1（GLUT 1）、血管内皮生长因子和水通道蛋白4。我们发现，HIF-1抑制导致运动功能恶化，病变体积增加，体温降低，水肿形成减少。所有这些参数在HA小鼠中均存在显著差异。Western印迹分析和酶联免疫吸附试验显示HA小鼠中所有HIF-1下游靶点的水平降低，然而，NT小鼠中仅GLUT 1下调。我们的结论是，HIF-1是一个关键的介质在自发恢复和HA诱导的神经保护TBI后。Journal of Cerebral Blood Flow & Metabolism（2013）33，524-531; doi：10.1038/jcbfm.2012.193; 2013年1月2日在线发表
Heat acclimation (HA), a well-established preconditioning model, confers neuroprotection in rodent models of traumatic brain injury (TBI). It increases neuroprotective factors, among them is hypoxia-inducible factor 1 alpha (HIF-1 alpha), which is important in the response to postinjury ischemia. However, little is known about the role of HIF-1a in TBI and its contribution to the establishment of the HA protecting phenotype. Therefore, we aimed to explore HIF-1 alpha role in TBI defense mechanisms as well as in HA-induced neuroprotection. Acriflavine was used to inhibit HIF-1 in injured normothermic (NT) or HA mice. After TBI, we evaluated motor function recovery, lesion volume, edema formation, and body temperature as well as HIF-1 downstream transcription targets, such as glucose transporter 1 (GLUT1), vascular endothelial growth factor, and aquaporin 4. We found that HIF-1 inhibition resulted in deterioration of motor function, increased lesion volume, hypothermia, and reduced edema formation. All these parameters were significantly different in the HA mice. Western blot analysis and enzyme-linked immunosorbent assay showed reduced levels of all HIF-1 downstream targets in HA mice, however, only GLUT1 was downregulated in NT mice. We conclude that HIF-1 is a key mediator in both spontaneous recovery and HA-induced neuroprotection after TBI. Journal of Cerebral Blood Flow & Metabolism (2013) 33, 524-531; doi:10.1038/jcbfm.2012.193; published online 2 January 2013