Nuclear factor-κB decoy attenuates neuronal damage after global brain ischemia:: A future strategy for brain protection during circulatory arrest

Objectives: Recent studies have reported that cis element decoy oligodeoxynucleotides against nuclear factor-kappaB block the activation of genes that mediate ischemic injury. To improve brain protection during circulatory arrest in cardiac surgery, we evaluated the efficacy of nuclear factor-kappaB decoy oligodeoxynucleotides in preventing neuronal damage after global brain ischemia. Methods: Hemagglutinating virus of Japan-liposome complex with fluorescein isothiocyanate-labeled nuclear factor-kappaB decoy oligodeoxynucleotides was injected through the carotid artery during 20 minutes or global brain ischemia in rats to evaluate the efficacy of transfecting the decoy oligodeoxynucleotides. The messenger RNA levels of several factors related to ischemia-reperfusion injury in the hippocampus were estimated by a real-time polymerase chain reaction method I hour after reperfusion. Neuronal damage was evaluated by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling staining and by using immunohistochemical study of microtubule-associated protein 2 in the hippocampus CA-1 region 7 days after ischemia, Results: Introduction of the nuclear factor-kappaB decoy oligodeoxynucleotides into rat brain neurons through the carotid artery during global brain ischemia was markedly successful. The polymerase chain reaction study showed that the transfected nuclear factor-kappaB decoy oligodeoxynucleotides effectively inhibited the expression of tumor necrosis factor alpha interleukin 1 beta and intracellular adhesion molecule I messenger RNA I hour after global brain ischemia. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling staining and microtubule-associated protein 2 immunohistochemistry showed that the transfected nuclear factor-kappaB decoy oligodeoxynucleotides significantly attenuated the neuronal damage 7 days after global brain ischemia. Conclusions: Therapeutic transfection of nuclear factor-kappaB decoy oligodeoxynucleotides during brain ischemia may be useful for attenuating neuronal damage, suggesting a strategy for cerebral protection against global ischemia.