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首页> 外文学位 >Elucidating the Role of Endogenous Electric Fields in Regulating the Astrocytic Response to Injury in the Mammalian Central Nervous System.
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Elucidating the Role of Endogenous Electric Fields in Regulating the Astrocytic Response to Injury in the Mammalian Central Nervous System.

机译：阐明内源性电场在调节哺乳动物中枢神经系统对损伤的星形胶质细胞反应中的作用。

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摘要

Endogenous bioelectric fields guide morphogenesis during embryonic development and regeneration by directly regulating the cellular functions responsible for these phenomena. Although this role has been extensively explored in many peripheral tissues, the ability of electric fields to regulate wound repair and stimulate regeneration in the mammalian central nervous system (CNS) has not been convincingly established. This dissertation explores the role of electric fields in regulating the injury response and controlling the regenerative potential of the mammalian CNS. We place particular emphasis on their influence on astrocytes, as specific differences in their injury-induced behaviors have been associated with differences in the regenerative potential demonstrated between mammalian and non-mammalian vertebrates. For example, astrocytes in both mammalian and non-mammalian vertebrates begin migrating towards the lesion within hours and begin to proliferate after an initial delay of two days; subsequently, astrocytes in non-mammalian vertebrates support neurogenesis and assume a bipolar radial glia-like morphology that guides regenerating axons, whereas astrocytes in mammals do not demonstrate robust neurogenesis and undergo a hypertrophic response that inhibits axon sprouting. To test whether injury-induced electric fields drive the astrocytic response to injury, we exposed separate populations of purified astrocytes from the rat cortex and cerebellum to electric field intensities associated with intact and injured mammalian tissues, as well as to those electric field intensities measured in regenerating non-mammalian vertebrate tissues. Upon exposure to electric field intensities associated with uninjured tissue, astrocytes showed little change in their cellular behavior. However, cortical astrocytes responded to electric field intensities associated with injured mammalian tissues by demonstrating dramatic increases in migration and proliferation, behaviors that are associated with their formation of a glial scar in vivo; in contrast, cerebellar astrocytes, which do not organize into a demarcated glial scar, did not respond to these electric fields. At electric field intensities associated with regenerating tissues, both cerebellar and cortical astrocytes demonstrated robust and sustained responses that included morphological changes consistent with a regenerative phenotype. These results support the hypothesis that physiologic electric fields drive the astrocytic response to injury, and that elevated electric fields may induce a more regenerative response among mammalian astrocytes.
机译：内源性生物电场通过直接调节负责这些现象的细胞功能来指导胚胎发育和再生过程中的形态发生。尽管已经在许多周围组织中广泛探索了这种作用，但尚未令人信服地建立电场调节伤口修复和刺激哺乳动物中枢神经系统（CNS）再生的能力。本文探讨了电场在调节哺乳动物中枢神经系统损伤反应和控制再生潜力中的作用。我们特别强调它们对星形胶质细胞的影响，因为它们在损伤诱导行为中的特定差异与哺乳动物和非哺乳动物脊椎动物之间表现出的再生潜能差异有关。例如，哺乳动物和非哺乳动物脊椎动物中的星形胶质细胞都在数小时内开始向病灶迁移，并在最初的两天延迟后开始增殖。随后，非哺乳动物脊椎动物中的星形胶质细胞支持神经发生，并呈现出引导再生轴突的双极放射状胶质样形态，而哺乳动物中的星形胶质细胞则没有表现出强大的神经发生性，并且不会抑制轴突发芽而发生肥大反应。为了测试损伤诱导的电场是否驱动星形胶质细胞对损伤的反应，我们将来自大鼠皮层和小脑的纯净星形胶质细胞群暴露于与完整和受伤的哺乳动物组织相关的电场强度，以及暴露于其中的电场强度。再生非哺乳动物脊椎动物组织。暴露于未受伤组织的电场强度后，星形胶质细胞的细胞行为几乎没有变化。然而，皮质星形胶质细胞通过显示出迁移和增殖的急剧增加来响应与受伤的哺乳动物组织相关的电场强度，这种行为与其在体内形成神经胶质疤痕有关。相反，没有组织成划定的神经胶质瘢痕的小脑星形胶质细胞对这些电场没有反应。在与再生组织相关的电场强度下，小脑和皮层星形胶质细胞均表现出强大而持续的反应，其中包括与再生表型一致的形态变化。这些结果支持以下假说：生理电场驱动对损伤的星形细胞反应，而升高的电场可能会在哺乳动物星形胶质细胞中诱导更多的再生反应。

著录项

  • 作者

    Baer, Matthew Louis.;

  • 作者单位

    Virginia Commonwealth University.;

  • 授予单位 Virginia Commonwealth University.;
  • 学科 Neurosciences.
  • 学位 Ph.D.
  • 年度 2015
  • 页码 360 p.
  • 总页数 360
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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