Activation of nuclear factor-kappa B in the rabbit spinal cord following ischemia and reperfusion

The transcription factor NF-kappa B is a ubiquitously expressed inducible r egulator of a broad range of genes. Recent studies have shown that activati on of NF-kappa B predominantly is associated with protecting cells from apo ptosis, but in some cell models, it is associated with promoting cell death . We used a rabbit spinal cord model of reversible ischemia to determine wh ether NF-kappa B was activated by ischemic and reperfusion injury. DNA bind ing activity of NF-kappa B was analyzed by an electrophoretic mobility shif t assay in animals subjected to varying durations of ischemia and reperfusi on. A low level of constitutive NF-kappa B DNA binding was detected in norm al lumbar spinal cord extracts. Animals subjected to a short ischemic insul t of 15 min, from which they usually recover neurologic function, had a sig nificant increase in the amount of active NF-kappa B in nuclear extracts af ter 18 h reperfusion. There was no change in nuclear NF-kappa B DNA binding in animals occluded for 60 min that are permanently paraplegic and exhibit extensive neuropathological damage. The amount of deoxycholate-releasable NF-kappa B sequestered in the cytosol, however, decreased after 18 h reperf usion in rabbits occluded for 60 min. This correlated with a decrease in th e amount of RelA(p65) NF-kappa B subunit. The results suggest that activati on of NF-kappa B after a limited ischemic injury may participate in a neuro protective response and not in cell death. (C) 1998 Elsevier Science B.V. A ll rights reserved.