HIF-1 alpha and VEGF expression after transient global cerebral ischemia

Hypoxia inducible factor-1 alpha (HIF-1 alpha) and vascular endothelial growth factor (VEGF) expression were studied in rat cerebral cortex after reversible global cerebral ischemia produced by cardiac arrest and resuscitation. Immunoblot analysis showed a significant induction of HIF-1 alpha protein after 1 hour of recovery from cardiac arrest which remained elevated for at least 12 hours. Upregulation of VEGF mRNA and protein were also observed but this was delayed in comparison to the HIF-1 alpha response. VEGF188 and VEGF164 mRNA levels were increased at 12-48 h of recovery from cardiac arrest but returned to basal expression after 7 days. Changes in VEGF120 mRNA expression did not reach statistical significance. Correspondingly, VEGF protein levels increased by about double at 24 and 48 hours of recovery but returned to basal levels after 7 days. These results suggest that cardiac arrest and resuscitation triggers HIF-1 alpha induction, which might be at least in part responsible for the stimulation of VEGF expression.