...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Molecular Neurobiology >Hypoxia-Preconditioned Human Umbilical Vein Endothelial Cells Protect Against Neurovascular Damage After Hypoxic Ischemia in Neonatal Brain
【24h】

Hypoxia-Preconditioned Human Umbilical Vein Endothelial Cells Protect Against Neurovascular Damage After Hypoxic Ischemia in Neonatal Brain

机译：缺氧预处理人脐静脉内皮细胞保护新生大脑缺氧缺血后神经血管损伤

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Therapy targeting the neurovascular unit may provide effective neuroprotection against neonatal hypoxia–ischemia (HI). We hypothesized that the peripheral injection of hypoxia-preconditioned human umbilical vein endothelial cells (HUVECs) following HI protects against neurovascular damage and provides long-term neuroprotection in a postpartum (P) day-7 rat pup model. Compared with normoxic HUVECs, hypoxic HUVECs showed enhanced migration and angiogenesis in vitro and had augmented migration effects into the brain when administered intraperitoneally in vivo after HI. Moreover, 24 and 72?h post-HI, the hypoxic HUVECs group but not the normoxic HUVECs or culture-medium groups had significantly higher preservation of microvessels and neurons, and attenuation of blood–brain barrier damage than the normal-saline group. Compared to control or normal-saline groups, only the hypoxic HUVECs group had no impaired foot steps and showed a significant reduction of brain area loss at P42. Next-generation sequencing showed hypoxia-induced upregulation and downregulation of 209 and 215 genes in HUVECs, respectively. Upstream regulator analysis by ingenuity pathway analysis (IPA) identified hypoxia-inducible factor 1-alpha as the key predicted activated transcription regulator. After hypoxia, 12 genes ( ADAMTS1 , EFNA1 , HIF1A , LOX , MEOX2 , SELE , VEGFA , VEGFC , CX3CL1 , HMMR , SDC , and SERPINE ) associated with migration and/or angiogenesis were regulated in HUVECs. In addition, 6 genes ( VEGFA , VEGFC , NTN4 , TGFA , SERPINE1 , and CX3CL1 ) involved in the survival of endothelial and neuronal cells were also markedly altered in hypoxic HUVECs. Thus, cell therapy by using hypoxic HUVECs that enhance migration and neurovascular protection may provide an effective therapeutic strategy for treating neonatal asphyxia.
机译：靶向神经血管单元的治疗可以为新生儿缺氧缺血（HI）提供有效的神经保护。我们假设缺氧预处理的人脐静脉内皮细胞（HUVEC）的外周注射可防止神经血管损伤，并在产后（P）日-7大鼠幼崽模型中提供长期神经保护。与常规Huvecs相比，缺氧Huvecs在体外显示出增强的迁移和血管生成，并且在Hi腹腔腹膜内施用时增加了迁移效应。此外，24和72？H HI后，缺氧HUVECS组但不是常氧HUVECS或培养基群体的保存明显高，保存微血管和神经元，并衰减血脑屏障损伤的损伤而不是常规盐水组。与对照或正常盐水组相比，只有缺氧Huvecs组没有受损的足部步骤，并且在P42下表现出大脑面积损失的显着降低。下一代测序显示出缺氧诱导的UPECS诱导的上调和下调209和215个基因。通过互联途径分析（IPA）鉴定缺氧诱导因子1-α作为关键预测活化转录调节剂的上游调节剂分析。在HUVEC中调节缺氧12基因（AdamTs1，EFNA1，HIF1A，LOX，MEOX2，SELE，VEGFA，VEGFC，CX3CL1，HMMR，SDC和血清）。此外，参与内皮和神经元细胞存活的6个基因（VEGFA，VEGFC，NTN4，TGFA，Serpine1和CX3Cl1）也显着改变了缺氧HUVEC。因此，通过使用缺氧HUVEC来增强迁移和神经血管保护的细胞治疗可以提供有效的治疗新生儿窒息的治疗策略。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号