Drug-induced neuroprotection from global ischemia is associated with prevention of persistent but not transient activation of nuclear factor-κB in rats

Abstract

Background and Purpose - Nuclear factor-κB (NF-κB) is an oxidative stress responsive transcription factor that is transiently activated in most forebrain neurons in response to transient global ischemia. However, in hippocampal CA1 neurons destined to die, NF-κB remains persistently activated. The present study was perforated to determine whether an antioxidant (LY231617) that afforded neuroprotection in previous studies had any effect on NF-κB activation in hippocampal CA1 neurons after global ischemia. Methods - Rats were subjected to 30 minutes of forebrain ischemia by 4-vessel occlusion (4-VO) and killed at 24 and 72 hours after ischemia. LY231617 was administered orally at a dose of 50 mg/kg 30 minutes before 4- VO and again 4 hours after 4-VO. Neuronal damage was evaluated in sections stained with cresyl violet. Other sections were immunostained with antibodies to NF-κB p50 to assess nuclear localization. An electrophoretic mobility shift assay was performed on nuclear extracts from sham- and LY231617- treated rats at 24 and 72 hours after ischemia. Results - The administration of LY231617 had a significant protective effect on hippocampal CA1 neurons at 72 hours after ischemia (control group, 16±7 neurons/mm; treated group, 294±35 neurons/mm, P