Cellular Indicators Of Neuronal Insult

脑内免疫/炎症反应的局部激活在急性脑损伤和可能的神经变性中起着重要作用。在没有外周免疫细胞的情况下，大脑的常驻免疫细胞提供了一个免疫网络。通过这个网络，各种细胞进行交流，并调节免疫和炎症反应的启动、传播和抑制的复杂过程。小胶质细胞是神经系统的主要细胞，在这种免疫反应中，它产生促炎细胞因子，并具有吞噬巨噬细胞样反应的能力。我们认为，了解了神经胶质细胞对急性损伤的反应和吞噬作用的启动的生物学过程，我们将揭示神经元和胶质细胞之间的关键相互作用，这种相互作用既适用于急性损伤，也适用于大脑中更进行性的神经退化过程。在过去的一年里，我们研究了各种炎症反应及其与神经细胞死亡模式的时间和空间联系。我们已经证明了在海马神经元死亡模型中驻留的小胶质细胞及其产生的肿瘤坏死因子α的主要作用。这些研究还表明，激活的小胶质细胞吞噬神经元碎片是后续修复过程的关键，包括用新生成的神经元重新填充海马齿状回。这些研究支持“炎症”在为神经元修复提供刺激环境方面的积极作用。这些研究对未来研究的设计具有影响，以检查增强大脑再生过程的过程，这些过程可能不仅适用于中风或头部创伤等急性损伤，而且可能适用于对更严重的神经退行性变的干预。

Local activation of an immune/inflammatory response in the brain plays a significant role in acute brain injury and possibly neurodegeneration. The resident immune cells of the brain provide an immune network in the absence of peripheral immune cells. Through this network, various cells communicate and regulate complex processes of initiation, propagation, and suppression of immune and inflammatory responses. The microglia is the primary cell of the nervous system considered in such an immune response in it's production of pro-inflammatory cytokines and it's ability to assume phagocytic macrophage-like responses. We propose that understanding biological processes underlying the glia response to actue injury and the initiation of phagocytosis we will uncover critical interactions between the neurons and the glia that can be applied to both acute injury as well as more progressive neurodegenerative processes in the brain. Over the past year we have examine various inflammatory responses and their temporal and spatial association with pattern of neuronal cell death. We have demonstrated a primary role of resident microglia cells and their production of tumor necrosis factor alpha in a model of neuronal death in the hippocampus. These studies have also suggested a critical need of phagocytosis of neuronal debris by activated microglia for subsequent repair processes including a repopulation of the hippocampal dentate gyrus with newly generated neurons. These studies support a positive role for "inflammation" in providing a stimulating environment for neuronal repair. Such studies have implications for the design of future studies to examine processes by which to enhance regenerative processes in the brain that may possibly be applied not only to acute injury such as stroke or head trauma, but may be applicable to intervention with regard to more progressive neurodegeneration.