Hypoxic-preconditioning enhances the regenerative capacity of neural stem/progenitors in subventricular zone of newborn piglet brain
Hypoxic-preconditioning enhances the regenerative capacity of neural stem/progenitors in subventricular zone of newborn piglet brain
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DOI：
10.1016/j.scr.2013.04.007
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发表时间：
2013-09-01
影响因子：
1.2
通讯作者：
De Montpellier, Sybille
中科院分区：
文献类型：
--
作者：
Ara, Jahan;De Montpellier, Sybille
围产期缺氧缺血（HI）导致脑损伤，而轻度缺氧事件导致预处理，这可以显着降低大脑的脆弱性，随后严重缺氧缺血。缺氧预处理（PC）已被证明可以增强中枢神经系统（CNS）祖细胞的存活和分化。本研究的目的是确定在HI之前用PC预处理是否刺激新生仔猪脑室下区（SVZ）的增殖和神经发生。将1日龄仔猪暴露于PC（8%O-2/92%N-2）3 h，24 h后暴露于缺氧（5%FiO（2））30 min和低血压诱导缺血10 min联合产生的HI。在这里，我们证明了SVZ衍生的神经干/祖细胞（NSP）从PC，HI和PC + HI仔猪增殖为神经球，表达神经祖细胞和神经发育标志物，和更大比例的球体产生的是多能的。神经球测定显示，预处理增加了NSP衍生的神经球在SVZ HI后相比，常氧和HI对照。来自预处理SVZ的NSP在体外产生两倍的神经元和星形胶质细胞。PC后注射5-溴-2-脱氧尿苷（BrdU）显示SVZ内持续一周的强烈增殖反应。PC还增加了体内神经发生，观察到具有迁移特征的doublecortin阳性细胞从SVZ流向纹状体和新皮质。这些结果表明，PC诱导的增殖和神经发生可能是一种积极的适应，在缺氧缺血损伤的情况下，有效的修复和可塑性。(C)2013爱思唯尔有限公司版权所有。
Perinatal hypoxia-ischemia (HI) results in brain injury, whereas mild hypoxic episodes result in preconditioning, which can significantly reduce the vulnerability of the brain to subsequent severe hypoxia ischemia. Hypoxic-preconditioning (PC) has been shown to enhance cell survival and differentiation of progenitor cells in the central nervous system (CNS). The purpose of this study was to determine whether pretreatment with PC prior to HI stimulates subventricular zone (SVZ) proliferation and neurogenesis in newborn piglets. One-day-old piglets were subjected to PC (8% O-2/92% N-2) for 3 h and 24 h later were exposed to HI produced by combination of hypoxia (5% FiO(2)) for a pre-defined period of 30 min and ischemia induced by a period of 10 min of hypotension. Here we demonstrate that SVZ derived neural stem/progenitor cells (NSPs) from PC, HI and PC + HI piglets proliferated as neurospheres, expressed neural progenitor and neurodevelopmental markers, and that greater proportion of the spheres generated are multipotential. Neurosphere assay revealed that preconditioning pretreatment increased the number of NSP-derived neurospheres in SVZ following HI compared to normoxic and HI controls. NSPs from preconditioned SVZ generated twice as many neurons and astrocytes in vitro. Injections with 5-Bromo-2-deoxyuridine (BrdU) after PC revealed a robust proliferative response within the SVZ that continued for one week. PC also increased neurogenesis in vivo, doublecortin positive cells with migratory profiles were observed streaming from the SVZ to striatum and neocortex. These findings show that the induction of proliferation and neurogenesis by PC might be a positive adaptation for an efficient repair and plasticity in the event of a hypoxic ischemic insult. (C) 2013 Elsevier B.V. All rights reserved.