Microglia are a major cell population in the central nervous system (CNS) that mediate inflammatory responses to brain injury. The ability to control microglial function would offer ways to reduce inflammation and enhance recovery of CNS function after trauma. Recently my laboratory has developed methods to identify, isolate, and characterize ameboid microglia obtained from the brain of newborn rat. Our work shows that ameboid microglia are a class of mononuclear phagocytes which may be distinguished from blood monocytes or peritoneal macrophages, that ameboid microglia release peptide factors which control the growth of astroglia, and that under certain conditions ameboid microglia will differentiate into process-bearing cells similar to ramified microglia found in adult brain. In vitro analysis demonstrates, moreover, that ameboid cells both produce and respond to several classes of immunomodulators. These observations are important ones for they suggest microglia as effector cells linking the immune system with brain development, inflammation, and glial scar formation. In order to extend our understanding of microglial biology, I propose to: 1) characterize the structure and composition of isolated ameboid and ramified microglia 2) isolate microglial growth factors 3) study growth and differientation of microglia in vivo 4) study microglial response to brain injury. The techniques needed to complete the proposed research include tissue culture, histology, cell isolations, surgical manipulation, and protein purification methodologies. If successful, this work will lead to new insights in such diverse areas as neuroimmunology and developmental neurobiology and will serve as a starting point for clinical trials to manipulate mononuclear phagocytes found in neurologic disease.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
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Neurology C Study Section (NEUC)
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Baylor College of Medicine
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Giulian, D; Yu, J; Li, X et al. (1996) Study of receptor-mediated neurotoxins released by HIV-1-infected mononuclear phagocytes found in human brain. J Neurosci 16:3139-53
Giulian, D; Haverkamp, L J; Li, J et al. (1995) Senile plaques stimulate microglia to release a neurotoxin found in Alzheimer brain. Neurochem Int 27:119-37
Giulian, D; Li, J; Bartel, S et al. (1995) Cell surface morphology identifies microglia as a distinct class of mononuclear phagocyte. J Neurosci 15:7712-26
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Giulian, D; Li, J; Li, X et al. (1994) The impact of microglia-derived cytokines upon gliosis in the CNS. Dev Neurosci 16:128-36
Giulian, D; Corpuz, M; Chapman, S et al. (1993) Reactive mononuclear phagocytes release neurotoxins after ischemic and traumatic injury to the central nervous system. J Neurosci Res 36:681-93
Giulian, D (1993) Reactive glia as rivals in regulating neuronal survival. Glia 7:102-10
Giulian, D; Vaca, K (1993) Inflammatory glia mediate delayed neuronal damage after ischemia in the central nervous system. Stroke 24:I84-90
Giulian, D; Vaca, K; Corpuz, M (1993) Brain glia release factors with opposing actions upon neuronal survival. J Neurosci 13:29-37
Giulian, D; Johnson, B; Krebs, J F et al. (1991) A growth factor from neuronal cell lines stimulates myelin protein synthesis in mammalian brain. J Neurosci 11:327-36

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