THE REGULATORY ROLE OF NF-κB IN AUTOPHAGY-LIKE CELL DEATH AFTER FOCAL CEREBRAL ISCHEMIA IN MICE

摘要: Autophagy may contribute to ischemia-induced cell death in the brain, but regulation of autophagic is largely unknown. Nuclear factor kappa B (NF-κB) a regulator apoptosis cerebral ischemia. We examined hypothesis that autophagy-like could brain damage and process was regulated by NF-κB. In adult wild-type (WT) NF-κB p50 knockout (p50(-/-)) mice, focal ischemia barrel cortex induced ligation distal branches middle artery. Twelve 24h later, activity increased as indicated enhanced expression Beclin-1 LC3 ischemic core and/or penumbra regions. This autophagy contributed injury, evidenced terminal deoxynucleotidyltransferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL) co-staining protective effect achieved inhibitor 3-methyladenine. The number Beclin-1/TUNEL-positive cells significantly more p50(-/-) mice than WT mice. Neuronal vascular death, determined TUNEL-positive with NeuN or Collagen IV, abundant Immunostaining endothelial tight junction marker occludin revealed blood-brain barrier Western blotting peri-infarct tissue showed reduction Akt-the mammalian target rapamycin (mTOR) signaling after These findings provide first evidence injury pathway, which suggest potential treatments for stroke.