Cellular Indicators Of Neuronal Insult

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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.