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The ischemic newborn brain: Endogenous response, functional deficits, and transplantation repair following stroke in the neonatal rat.

机译:新生儿缺血性脑:新生大鼠中风后的内源性反应,功能缺陷和移植修复。

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摘要

In the clinical setting, ischemic stroke within the neonatal period may result in significant morbidity and mortality immediately following the event or go unrecognized until developmental delays present themselves much later; smaller cortical insults in particular frequently manifest with mild delay or attention or learning deficits. This dissertation explores the mechanisms by which the ischemic newborn rat brain attempts to self-repair following insult, the degree of functional deficit that is observed in our new rat model of neonatal ischemia, and a novel strategy for therapeutic stem cell transplantation. Here, we report a novel pro-migratory mechanism for subventricular zone neuroblast migration toward the ischemic boundary via the VEGF-VEGFR-2 pathway using an ischemia-only rat model. We further assess the degree and extent of functional deficits generated by our ischemia-only neonatal model with regard to developmental milestones and sensory and motor development. We report that ischemic stroke induces significant effects on sensory and motor function in addition to delaying certain developmental milestones in the rat pup. We also report that stroke results in gender-dependent effects for certain functional measurements. Finally, we introduce the utility of transplanted of hypoxically-preconditioned bone marrow stromal cells to further support the endogenous repair process that we have shown occurs after neonatal ischemic stroke. We demonstrate that hypoxic preconditioning up-regulates pro-angiogenic trophic, adhesion, support, and signaling mediators in vitro. Further, when these cells are transplanted in the ischemic neonatal rat, we show that these cells maintain an up-regulated pro-angiogenic expression profile that likely forms an improved support structure and a trophic foundation for enhanced endogenous neurogenesis and structural repair.
机译:在临床情况下,新生儿期缺血性中风可能导致事件发生后立即发生大量的发病和死亡,或者直到很晚出现发育迟缓才被人们所认识。较小的皮质损伤尤其表现为轻度延迟或注意力或学习障碍。本文探讨了缺血性新生大鼠脑在受到损伤后试图自我修复的机制,在我们的新生大鼠缺血模型中观察到的功能缺陷程度以及一种治疗性干细胞移植的新策略。在这里,我们报告了一种新的促迁移机制,使用仅缺血的大鼠模型,通过VEGF-VEGFR-2途径使脑室下区成神经细胞向缺血边界迁移。我们进一步评估了我们的仅缺血新生儿模型在发育里程碑,感觉和运动发展方面所产生的功能缺陷的程度和程度。我们报告说,缺血性中风除了延迟大鼠幼仔的某些发育里程碑外,还对感觉和运动功能产生重大影响。我们还报告说,中风导致某些功能测量的性别依赖性效应。最后,我们介绍了经过缺氧预处理的骨髓基质细胞移植的实用程序,以进一步支持我们已经证明新生儿缺血性中风后发生的内源性修复过程。我们证明低氧预处理可在体外调节促血管生成的营养,粘附,支持和信号传导介体。此外,当将这些细胞移植到缺血性新生大鼠中时,我们显示这些细胞维持了上调的促血管生成表达谱,它可能形成改善的支持结构和营养基础,从而增强了内源性神经发生和结构修复。

著录项

  • 作者

    Fraser, Jamie L.;

  • 作者单位

    Medical University of South Carolina.;

  • 授予单位 Medical University of South Carolina.;
  • 学科 Biology Molecular.;Biology Cell.;Biology Neuroscience.
  • 学位 Ph.D.
  • 年度 2010
  • 页码 320 p.
  • 总页数 320
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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