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The Journal of Immunology, Vol 149, Issue 8 2736-2741, Copyright © 1992 by American Association of Immunologists
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CC Chao, S Hu, TW Molitor, EG Shaskan and PK Peterson
Neuroimmunobiology and Host Defense Laboratory, Minneapolis Medical Research Foundation, MN 55404.
Activated microglial have been proposed to play a pathogenetic role in immune-mediated neurodegenerative diseases. To test this hypothesis, purified murine neonatal microglial were cocultured with neuronal cells derived from fetal brain. Activation with IFN-gamma and LPS of these cocultures brought about a sharp decrease in uptake of gamma-amino butyric acid and a marked reduction in neuronal cell survival. These effects varied with the density of microglia, the concentrations of the activation signals (IFN-gamma and LPS), and the duration of coculture. Inasmuch as addition of NG-monomethyl-L-arginine blocked these effects, a L-arginine-dependent neurocytotoxic mechanism was implicated. Abundant nitrite, a metabolite of the free radical nitric oxide (NO) derived from L-arginine, was detected in activated microglial/neuronal cell cocultures and in purified microglial cell cultures but not in purified astrocyte or neuronal cell cultures, suggesting that microglial were the principal source of the NO. These findings support the hypothesis that microglia are the source of a neurocytotoxic-free radical, and shed light on an additional mechanism of immune-mediated brain injury.
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L.-Y. Kong, M. K. McMillian, P. M. Hudson, L. Jin, and J.-S. Hong Inhibition of Lipopolysaccharide-Induced Nitric Oxide and Cytokine Production by Ultralow Concentrations of Dynorphins in Mixed Glia Cultures J. Pharmacol. Exp. Ther., January 1, 1997; 280(1): 61 - 66. [Abstract] [Full Text]
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M. Mori, M. Aihara, K. Kume, M. Hamanoue, S. Kohsaka, and T. Shimizu Predominant Expression of Platelet-Activating Factor Receptor in the Rat Brain Microglia J. Neurosci., June 1, 1996; 16(11): 3590 - 3600. [Abstract] [Full Text] [PDF]
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S. Murphy and D. Grzybicki {blacksquare} REVIEW : Glial NO: Normal and Pathological Roles Neuroscientist, March 1, 1996; 2(2): 90 - 99. [Abstract] [PDF]
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J. Hu, F. Castets, J. L. Guevara, and L. J. Van Eldik S100beta Stimulates Inducible Nitric Oxide Synthase Activity and mRNA Levels in Rat Cortical Astrocytes J. Biol. Chem., February 2, 1996; 271(5): 2543 - 2547. [Abstract] [Full Text] [PDF]
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M. Colasanti, T. Persichini, M. Menegazzi, S. Mariotto, E. Giordano, C. M. Caldarera, V. Sogos, G. M. Lauro, and H. Suzuki Induction of Nitric Oxide Synthase mRNA Expression J. Biol. Chem., November 10, 1995; 270(45): 26731 - 26733. [Abstract] [Full Text] [PDF]
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