Cited by 786

Microglial-produced nitric oxide and reactive nitrogen oxides mediate neuronal cell death

Boje, Kathleen M., Arora, Prince K.·1992·Brain Research

Abstract

The role of inflammatory cytokines in the pathogenesis of neurological diseases is not well understood. The neurotoxic effects of cytokines could be mediated by immunostimulation of glial cells to produce toxic concentrations of nitric oxide (NO) and reactive nitrogen oxides. Cultured microglia and meningeal fibroblasts, but not Type 1 astrocytes, were induced by lipopolysaccharides and cytokines to synthesize NO and reactive nitrogen oxides from L-arginine. In co-cultures of immunostimulated microglia and cerebellar granule neurons, neurotoxicity was blocked by an inhibitor of NO synthase, NG-nitroarginine, and by oxyhemoglobin, which inactivates NO. Microglial-induced neurotoxicity was also partially attenuated by the N-methyl-D-aspartate (NMDA) receptor antagonists, MK-801 and 2-amino-5-phosphovalerate (APV). Superoxide dismutase, which stabilizes NO through inactivation of superoxide anion, augmented microglial-mediated neurotoxicity either alone or in combination with MK-801 or APV. Hence, immunostimulated microglia mediate neurotoxicity by NO, reactive nitrogen oxides, superoxide anion and NMDA-like substances. These findings suggest a novel role for microglial-produced NO and reactive nitrogen oxides as a neurotoxic agent in neurodegenerative disease states.

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Crossref · 10.1016/0006-8993(92)91004-x

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Authors
Boje, K. M., & Arora, P. K.
Venue
Brain Research
Publisher
Elsevier BV
Published
1992-08
Volume
587
Issue
2
Pages
250-256
ISSN
0006-8993
Cited by
786
References
2
Language
en

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