Extracellular signal-regulated kinase involved in NGF/VEGF-induced neuroprotective effect

Objective To investigate the effect of the expression of extracellular signal-regulated kinase 1(ERK1) on cerebral ischemic injury, temporospatial alterations of ERK1 immunoreactivity in hippocampus and perifocal cortex and the expression involved in NGF/VEGF-induced neuroprotective effect were examined. Methods Focal cerebral ischemia/reperfusion model in rabbits was induced by transient occlusion of middle cerebral artery (MCAO). All rabbits were randomly divided into three groups: sham-operated group (n=6), ischemia/reperfusion group (n=60), factor-treated group (n=40). We measured the dynamic expression of ERK1 in hippocampus and perifocal cortex in rabbits exposed to focal cerebral ischemia and reperfusion by immuohistochemistry. Expression of caspase-3, apoptosis and ultrastructure were also evaluated by immunohistochemistry, flow cytometry analysis and electron microscopy. Results ERK1 expression was first increased in hippocampal CA3/DG 1 hours after reperfusion. At 6 hours after reperfusion ERK1 expression was also increased in other brain regions, with peak formed at day 1 to day 3, and then gradually decreased to basal level at day 14 after reperfusion. The expression of caspase-3 also was strongly activated 1h after reperfusion, with peak demonstrated at 3 days. NGF/VEGF significantly inhibited the expression of ERK1 and caspase-3. Conclusions These results suggest that ERK signaling pathway was involved in neuronal cell death and NGF/VEGF-induced neuroprotective effect by modifying death receptor pathway. Inhibition of ERK signaling pathway might therefore provide an efficient way for preventing neuronal cell death after cerebral ischemia.