Nuclear factor-κB activation during cerebral reperfusion: Effect of attenuation with N-acetylcysteine treatment

James Edwin Carroll, Eugene F. Howard, David C Hess, Chandramohan G. Wakade, Qiang Chen, Charles Cheng

Research output: Contribution to journalArticle

91 Scopus citations

Abstract

We examined activation of the transcription factor, nuclear factor-κB (NF-κB), which participates in the upregulation of endothelial cell adhesion proteins, during reperfusion after temporary middle cerebral artery occlusion (TMCAO). We hypothesized that N-acetylcysteine (NAC), an antioxidant which inhibits NF-κB activation, would alter events in brain reperfusion injury. We used a rat model of TMCAO. The left sides of the brains were rendered ischemic for 2 h, and then the area was allowed to reperfuse. The animals were treated with NAC (150 mg/kg) or saline placebo, sacrificed, and activated MF-κB was assessed in both the left and right hemispheres, all at varying intervals. Cerebral infarction volume was also measured in each of the hemispheres collected from a separate group of animals. Activated NF-κB, consisting of p65 and p50 Rel proteins, was significantly increased 15 min after reperfusion in the affected hemisphere. The activation at 15 min was completely abolished with NAC treatment. NAC treatment 1 h prior to the end of occlusion and at 24 h reduced the percentage infarction volume of the affected hemispheres from 35.5 ± 2.8% (S.E.) to 18.1 ± 2.1% (p < 0.01). NAC treatment at 1 h after the occlusion (after the NF-κB peak) and again at 24 h also significantly reduced the percentage infarction volume from 34.8 ± 3.8% to 24.6 ± 3.8% (p < 0.05). Thus, while NAC inhibited activation of NF-κB at 15 min after reperfusion, the drug acted to reduce cerebral infarction by additional, undefined mechanisms. These results bring into question the various roles of NF-κB in cerebral infarction followed by reperfusion.

Original languageEnglish (US)
Pages (from-to)186-191
Number of pages6
JournalMolecular Brain Research
Volume56
Issue number1-2
DOIs
StatePublished - May 1 1998

Keywords

  • Antioxidant
  • Cerebral infarction
  • Endothelial cell adhesion molecule
  • N-acetylcysteine
  • Nuclear factor-κB

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

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