Hypoxic-preconditioning induces neuroprotection against hypoxia-ischemia in newborn piglet brain

Hypoxic-preconditioning induces neuroprotection against hypoxia-ischemia in newborn piglet brain
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DOI:
10.1016/j.nbd.2011.04.021
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发表时间:
2011-08-01
影响因子:
6.1
通讯作者:
Valencia, Ignacio
Valencia, Ignacio
中科院分区:
医学1区
文献类型:
--
作者:
Ara, Jahan;Fekete, Saskia;Valencia, Ignacio

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预处理诱导的缺血耐受已在新生儿脑中被证实,然而,这种预处理的信号转导机制需要进一步阐明。本研究的目的是开发一种缺氧预处理(PC)模型的缺血耐受性的新生仔猪,模仿重要的临床相似性,人类的情况下出生窒息,并表征一些分子机制表明,参与PC诱导的神经保护啮齿动物模型。将一日龄仔猪置于PC(8% O(2)/92% N(2))中3 h,24 h后暴露于缺氧(5% FiO(2))30 min和低血压(平均动脉血压降低10 min;基线的70%)诱导的缺血联合引起的缺氧-缺血(HI)中。在HI后恢复24小时、3天和7天时进行的神经病理学分析和无偏倚体视学研究表明,与非PC仔猪相比,PC仔猪脑损伤的严重程度显著降低(P
Preconditioning-induced ischemic tolerance has been documented in the newborn brain, however, the signaling mechanisms of this preconditioning require further elucidation. The aims of this study were to develop a hypoxic-preconditioning (PC) model of ischemic tolerance in the newborn piglet, which emulates important clinical similarities to human situation of birth asphyxia, and to characterize some of the molecular mechanisms shown to be implicated in PC-induced neuroprotection in rodent models. One day old piglets were subjected to PC (8% O(2)/92% N(2)) for 3 h and 24 h later were exposed to hypoxia-ischemia (HI) produced by a combination of hypoxia (5% FiO(2)) for a period of 30 min and ischemia induced by a period of hypotension (10 min of reduced mean arterial blood pressure; 70% of baseline). Neuropathologic analysis and unbiased stereology, conducted at 24 h, 3 and 7 days of recovery following HI, indicated a substantial reduction in the severity of brain damage in PC piglets compared to non-PC piglets (P