Glia are thought to play an important role in determining the success or failure of axonal growth. For example, primitive glia in the developing nervous system are believed to guide growing axons and assist in neuronal migrations. In contrast, astroglia found at sites of injury in mammalian adult brain are thought to retard or inhibit axonal regeneration. The factors which regulate glial support of neurons are poorly understood. We have recently identified Interleukin-1 (IL-1) as a potent mitogen for astroglia. IL-1 is a pluripotent growth factor, released by mononuclear phagocytes, which affects the inflammatory process. Our findings show that IL-1 levels in the brain are elevated following injury or during early development, and suggest an important regulatory relationship between brain IL-1 and astroglia. We believe that release of IL-1 helps to control the proliferation, growth and differentiation of astroglia in the developing and injured CNS. We propose to characterize the role of IL-1 in the developing brain by measuring the IL-1 levels during embryogenesis, by identifying cells that secrete IL-1, by monitoring growth effects of IL-1 upon embryonic brain glia in vitro, and by monitoring glial growth in vivo in developing brain after IL-1 injections. We will investigate the significance of IL-1 in the brain during injury and disease by measuring IL-1 production after brain infarction, by measuring IL-1 production after axonal degeneration, by measuring IL-1 production after brain inflammation, and by monitoring glial growth in vivo in adult brain after IL-1 injections. We will also examine in vitro the effects of IL-1 upon glia by monitoring protease production in astroglia, by monitoring effects of IL-1 upon glial cells, and by screening for IL-1 dependent astroglial cell lines. If astroglia do in fact mediate neuronal development and axonal growth, peptides that control astroglial populations become clinically important. Therapies to accelerate axonal outgrowth or reduce glial scarring might arise from IL-1 related research.
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