ASTROGLIAL REACTION TO ISCHEMIC BRAIN INJURY

星形胶质细胞是高度互动和反应性强的脑细胞 对大脑功能至关重要。相应地，对大脑的损害将演变为 直接从损伤到星形胶质细胞或这些细胞会修改它们的 对邻近细胞损伤的反应行为。审查如何 星形胶质细胞对脑缺血损伤的反应应导致改善 对这种疾病的细胞发病机制的理解。这一哲学 指导这个项目的长期目标：了解星形胶质细胞如何 对缺血性脑损伤的反应以及酸碱波动如何参与 在他们的回应中。 星形胶质细胞要么因严重缺血(即脑梗塞)而退化，要么 通过减少流动的致命性而转化为活性物质。 这两个细胞的生理信息很少。 改变或暗示引起改变的原因。由于H I和K I 在真核细胞中调节生命活动，在 星形胶质细胞，是受这些细胞调控的两个主要离子物种， 星形胶质细胞HI和Ki变化与缺血性损伤的关系 将在这里详细介绍。离子选择性微电极测定pH、K、 以及最新开发的三管微电极阵列传感器 PH和CO32，将被用来关联星形细胞酸的模式- 脑缺血时碱、钾的变化与结构性改变 这些细胞的标记(即对细胞体大小、程度的测量 DNA复制、GFAP染色强度和分布以及 区域脑内GFAP含量的变化)。星形胶质细胞的退化将是 在活体中使用这种类型的局灶性脑梗塞的啮齿动物模型进行研究 缺血性脑损伤在临床上最为常见。星形胶质细胞变成 严重的酸中毒，并在全球范围内的脑梗塞期间失去它们的进程 缺血，可能是因为[HCO3-]i的严重减少。 局灶性脑梗塞的星形细胞pH值、[HCO3-]i和形态改变 未知，并将被确定。H_I和K_I的星形细胞改变 与反应性星形细胞增多症相关的研究将在体内进行，使用Global 并与星形细胞增多症的上述结构标志物相关。 此外，低温可以延缓神经元的破坏。 来自全球缺血，关于离子和结构变量与 反应性星形细胞增多症将被检查，因为这种破坏被认为是 是星形细胞增殖所必需的。此外，由于星状星云 PHI在反应性星形细胞增多症开始时升高，高碳酸血症的影响， 我们将对这些细胞的酸化进行研究。最后，体外脑 将切片制备用于测定以质膜为主的 星形胶质细胞PHI和KI变化相互关联的机制。

Astrocytes are highly interactive and reactive brain cells that are essential for brain function. Accordingly, damage to brain will evolve directly from injury to astrocytes or these cells will modify their behavior in response to injury of adjacent cells. Examination of how astrocytes respond to injury from brain ischemia should lead to an improved understanding of the cellular pathogenesis of this malady. This philosophy guides the long term goal of this project: To understand how astrocytes respond to ischemic brain injury and how acid-base fluctuations participate in their response. Astrocytes either degenerate from severe ischemia (i.e. infarction) or they are transformed into reactive species by less lethal reduction in flow. Little physiologic information exists that characterizes these two cell changes or alludes to what causes the alterations. Since H+i and K+i modulate vital activities in eukaryotic cells, are interrelated in astrocytes, and are two principal ionic species regulated by these cells, the interrelation of changes in astrocytic H+i and K+i to ischemic injury will be examined in detail here. Ion-selective microelectrodes for pH, K+, as well as a newly developed triple barrel microelectrode array sensitive to pH & CO32, will be used to correlate the patterns of astrocytic acid- base and K+ change from ischemia that are associated with structural markers for these cells (i.e measurements of the cell body size, degree of DNA replication, intensity and distribution of GFAP staining as well as change in regional brain GFAP content). Degeneration of astrocytes will be studied in vivo using a rodent model of focal infarction since this type of ischemic brain injury is clinically most prevalent. Astrocytes become severely acidotic and lose their processes during infarction from global ischemia, perhaps because of a critical reduction in [HCO3-]i. How astrocytic pHi, [HCO3-]I and morphology change with focal infarction is unknown and will be determined. Astrocytic changes in H+i and K+i associated with reactive astrocytosis will be studied in vivo using global ischemia and correlated to the above structural markers of astrocytosis. Furthermore, the effect of hypothermia, which retards neuronal destruction from global ischemia, on ionic and structural variables associated with reactive astrocytosis will be examined since such destruction is thought to be necessary for astrocytic proliferation. Additionally, since astroglial pHi rises at the onset of reactive astrocytosis, the effect of hypercarbia, which acidifies these cells will be studied. Finally, the in vitro brain slice preparation will be used to determine plasma membrane-based mechanisms which interrelate changes in astrocytic pHi and K+i.