TY - JOUR
T1 - Nuclear factor-κB activation during cerebral reperfusion
T2 - Effect of attenuation with N-acetylcysteine treatment
AU - Carroll, James E.
AU - Howard, Eugene F.
AU - Hess, David C.
AU - Wakade, C. G.
AU - Chen, Qiang
AU - Cheng, Charles
N1 - Funding Information:
This study was supported by the American Heart Association, Georgia Affiliate, and the V.A. Medical Research Service. We thank John Keel, Jay Melvin and Ashley Stone for assistance with the image analyses and Julie A. Mobley (Biostatistics) for her assistance with the statistical analyses.
PY - 1998/5
Y1 - 1998/5
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
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U2 - 10.1016/S0169-328X(98)00045-X
DO - 10.1016/S0169-328X(98)00045-X
M3 - Article
C2 - 9602121
AN - SCOPUS:0008587780
SN - 0169-328X
VL - 56
SP - 186
EP - 191
JO - Molecular Brain Research
JF - Molecular Brain Research
IS - 1-2
ER -