NUCLEAR FACTOR-KAPPA-B ACTIVATION DURING CEREBRAL REPERFUSION - EFFECT OF ATTENUATION WITH N-ACETYLCYSTEINE TREATMENT

We examined activation of the transcription factor, nuclear factor-kap pa B (NF-kappa B), which participates in the upregulation of endotheli al cell adhesion proteins, during reperfusion after temporary middle c erebral artery occlusion (TMCAO). We hypothesized that N-acetylcystein e (NAC), an antioxidant which inhibits NF-kappa B activation, would al ter 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 NF-kappa B was assessed in both the left and right hemispheres, all at varying inter vals. Cerebral infarction volume was also measured in each of the hemi spheres collected from a separate group of animals. Activated NF-kappa B, consisting of p65 and p50 Rel proteins, was significantly increase d 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 in farction 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-kappa B peak) and again at 24 h also significantly reduc ed the percentage infarction volume from 34.8 +/- 3.8% to 24.6 +/- 3.8 % (p < 0.05). Thus, while NAC inhibited activation of NF-kappa B at 15 min after reperfusion, the drug acted to reduce cerebral infarction b y additional, undefined mechanisms. These results bring into question the various roles of NF-kappa B in cerebral infarction followed by rep erfusion. (C) 1998 Elsevier Science B.V.