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

90 Citations (Scopus)

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

Fingerprint

Acetylcysteine
Reperfusion
Cerebral Infarction
Middle Cerebral Artery Infarction
Infarction
Therapeutics
Reperfusion Injury
Cell Adhesion
Brain Injuries
Proteins
Transcription Factors
Up-Regulation
Endothelial Cells
Antioxidants
Placebos
Brain
Pharmaceutical Preparations

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

Cite this

Nuclear factor-κB activation during cerebral reperfusion : Effect of attenuation with N-acetylcysteine treatment. / Carroll, James Edwin; Howard, Eugene F.; Hess, David C; Wakade, Chandramohan G.; Chen, Qiang; Cheng, Charles.

In: Molecular Brain Research, Vol. 56, No. 1-2, 01.05.1998, p. 186-191.

Research output: Contribution to journalArticle

@article{5453593cc5a846f1b35750497be67215,
title = "Nuclear factor-κB activation during cerebral reperfusion: Effect of attenuation with N-acetylcysteine treatment",
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.",
keywords = "Antioxidant, Cerebral infarction, Endothelial cell adhesion molecule, N-acetylcysteine, Nuclear factor-κB",
author = "Carroll, {James Edwin} and Howard, {Eugene F.} and Hess, {David C} and Wakade, {Chandramohan G.} and Qiang Chen and Charles Cheng",
year = "1998",
month = "5",
day = "1",
doi = "10.1016/S0169-328X(98)00045-X",
language = "English (US)",
volume = "56",
pages = "186--191",
journal = "Brain Research",
issn = "0006-8993",
publisher = "Elsevier",
number = "1-2",

}

TY - JOUR

T1 - Nuclear factor-κB activation during cerebral reperfusion

T2 - Effect of attenuation with N-acetylcysteine treatment

AU - Carroll, James Edwin

AU - Howard, Eugene F.

AU - Hess, David C

AU - Wakade, Chandramohan G.

AU - Chen, Qiang

AU - Cheng, Charles

PY - 1998/5/1

Y1 - 1998/5/1

N2 - 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.

AB - 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.

KW - Antioxidant

KW - Cerebral infarction

KW - Endothelial cell adhesion molecule

KW - N-acetylcysteine

KW - Nuclear factor-κB

UR - http://www.scopus.com/inward/record.url?scp=0008587780&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0008587780&partnerID=8YFLogxK

U2 - 10.1016/S0169-328X(98)00045-X

DO - 10.1016/S0169-328X(98)00045-X

M3 - Article

VL - 56

SP - 186

EP - 191

JO - Brain Research

JF - Brain Research

SN - 0006-8993

IS - 1-2

ER -