Vascular endothelial growth factor upregulation in transient global ischemia induced by cardiac arrest and resuscitation in rat brain

Abstract

This study examined vascular endothelial growth factor (VEGF) expression in rat brain after reversible global cerebral ischemia produced by cardiac arrest and resuscitation. Three alternative splicing forms, VEGF 188, VEGF 164 and VEGF 120, were observed in cortex, hippocampus and brainstem by RT–PCR analysis. After 24 h of recovery from cardiac arrest, mRNA levels corresponding to VEGF 188 and VEGF 164 were significantly increased by about double in all the regions analyzed. These mRNA levels remained elevated at 24 and 48 h of recovery but returned to basal expression after 7 days of recovery. Changes in VEGF 120 expression after cardiac arrest did not reach statistical significance. VEGF protein expression measured by Western blot was also increased by about double at 24 and 48 h of recovery but returned to control levels after 7 days of recovery. VEGF immunohistochemistry localized this increased expression mostly associated with astrocytes. Considering its biological activity, VEGF induction after cardiac arrest and resuscitation may be responsible for the increased vascular permeability and the resultant vasogenic edema, found 24–48 h after reversible global ischemia.