We have found that reactive microglia and invading macrophages exacerbate many neuropathic conditions including stroke and trauma. Moreover, drug inhibition of mononuclear phagocytes reduces neuronal loss and improves neurologic function. In order to understand and control inflammatory responses after acute CNS injury, we will study fundamental issues of microglial biology by comparing microglia with other classes of mononuclear phagocytes, by identifying activators and inhibitors of microglia function, and by delineating microglia-astroglia and microglia-neuron interactions. Bulk isolation of highly enriched populations of microglia will provide material needed to develop cell specific monoclonal antibodies. These reagents will then be used to monitor subclasses of mononuclear phagocytes after brain injury. Transplantation of prelabeled microglia will allow investigation of the functional capacities and fates of brain mononuclear phagocytes in vivo. Biochemical studies will include structural analysis of a brain-derived microglial mitogen as well as study of cytotoxic and neuro-excitant factors. In vitro and in vivo models will be used to explore the action of cytokines upon microglial cells and to screen immunosuppressive drug effects upon brain inflammation. We believe that these proposed experiments will uncover new and important roles for brain mononuclear phagocytes and, thus, provide new and important insights concerning immunologic events that regulate the structure and function of the CNS.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS025637-07
Application #
2265614
Study Section
Neurology C Study Section (NEUC)
Project Start
1988-02-01
Project End
1995-01-31
Budget Start
1994-02-01
Budget End
1995-01-31
Support Year
7
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Baylor College of Medicine
Department
Neurology
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; 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; 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; 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) A growth factor from neuronal cell lines stimulates myelin protein synthesis in mammalian brain. J Neurosci 11:327-36

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