Activated microglia mediate neuronal cell injury via a nitric oxide mechanism - PubMed (original) (raw)

. 1992 Oct 15;149(8):2736-41.

Affiliations

PMID: 1383325

Activated microglia mediate neuronal cell injury via a nitric oxide mechanism

C C Chao et al. J Immunol. 1992.

Abstract

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.

PubMed Disclaimer

Cited by

Green Tea Extract Ameliorates Learning and Memory Deficits in Ischemic Rats via Its Active Component Polyphenol Epigallocatechin-3-gallate by Modulation of Oxidative Stress and Neuroinflammation.
Wu KJ, Hsieh MT, Wu CR, Wood WG, Chen YF. Wu KJ, et al. Evid Based Complement Alternat Med. 2012;2012:163106. doi: 10.1155/2012/163106. Epub 2012 Aug 2. Evid Based Complement Alternat Med. 2012. PMID: 22919410 Free PMC article.
Sinomenine, a natural dextrorotatory morphinan analog, is anti-inflammatory and neuroprotective through inhibition of microglial NADPH oxidase.
Qian L, Xu Z, Zhang W, Wilson B, Hong JS, Flood PM. Qian L, et al. J Neuroinflammation. 2007 Sep 19;4:23. doi: 10.1186/1742-2094-4-23. J Neuroinflammation. 2007. PMID: 17880684 Free PMC article.
Periventricular leucomalacia: a review.
Blumenthal I. Blumenthal I. Eur J Pediatr. 2004 Aug;163(8):435-42. doi: 10.1007/s00431-004-1477-y. Epub 2004 Jun 4. Eur J Pediatr. 2004. PMID: 15179510 Review.
Effect of Chronic Administration of Nickel on Affective and Cognitive Behavior in Male and Female Rats: Possible Implication of Oxidative Stress Pathway.
Lamtai M, Chaibat J, Ouakki S, Zghari O, Mesfioui A, El Hessni A, Rifi EH, Marmouzi I, Essamri A, Ouichou A. Lamtai M, et al. Brain Sci. 2018 Jul 31;8(8):141. doi: 10.3390/brainsci8080141. Brain Sci. 2018. PMID: 30065183 Free PMC article.
The effects of NOS2 gene deletion on mice expressing mutated human AbetaPP.
Colton CA, Wilcock DM, Wink DA, Davis J, Van Nostrand WE, Vitek MP. Colton CA, et al. J Alzheimers Dis. 2008 Dec;15(4):571-87. doi: 10.3233/jad-2008-15405. J Alzheimers Dis. 2008. PMID: 19096157 Free PMC article. Review.

Activated microglia mediate neuronal cell injury via a nitric oxide mechanism - PubMed (original) (raw)