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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS025637-03
Application #
3410950
Study Section
Neurology C Study Section (NEUC)
Project Start
1988-02-01
Project End
1991-01-31
Budget Start
1990-02-01
Budget End
1991-01-31
Support Year
3
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Baylor College of Medicine
Department
Type
Schools of Medicine
DUNS #
074615394
City
Houston
State
TX
Country
United States
Zip Code
77030
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
Giulian, D; Li, J; Leara, B et al. (1994) Phagocytic microglia release cytokines and cytotoxins that regulate the survival of astrocytes and neurons in culture. Neurochem Int 25:227-33
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) Microglial mitogens are produced in the developing and injured mammalian brain. J Cell Biol 112:323-33

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