RAPID INDUCTION OF VASCULAR ENDOTHELIAL GROWTH-FACTOR GENE-EXPRESSIONAFTER TRANSIENT MIDDLE CEREBRAL-ARTERY OCCLUSION IN RATS

Background and Purpose Vascular endothelial growth factor (VEGF) is a mitogen for endothelial cells and also has the potential to increase v ascular permeability. Therefore, it may contribute to the recovery of brain cells from ischemic insult through potentiating neovascularizati on or may exacerbate brain damage by forming brain edema. However, the exact role of this protein in cerebral ischemia is not fully understo od. We investigated temporal, spatial, and cellular profiles of the in duction of VEGF gene expression after transient focal cerebral ischemi a at both mRNA and protein levels. Methods We used a transient middle cerebral artery (MCA) occlusion model. Northern blot analysis was perf ormed to assess the chronological pattern of induction and the impact of length of ischemia on mRNA expression. Western blot analysis was pe rformed to ensure the selective detection of immunoreactive VEGF with an antibody. Temporal, spatial, and cellular changes of immunohistoche mical VEGF expression were compared with different periods of reperfus ion from 1 hour to 7 days after transient MCA occlusion. Results (1) N orthern blot analysis revealed no detectable VEGF mRNA in the control brains. The mRNA became evident at 1 hour after reperfusion, peaked at 3 hours, and then decreased. The length of ischemia from 1 to 3 hours made no differences in the degree and temporal profile of the subsequ ent induction of VEGF mRNA. (2) Western blot analysis showed no band i n the control brain, but two bands with molecular weights of 38 and 45 kD, corresponding to VEGF(121) and VEGF(165), were induced at 1 hour of reperfusion, peaked at 3 hours of reperfusion, and then decayed. (3 ) Neurons in the cerebral cortex of the MCA territory expressed VEGF a t 1 hour after reperfusion with a peak at 3 hours and then diminished by 1 day. Pial cells of the MCA territory also expressed immunoreactiv e VEGF from 1 hour of reperfusion that was sustained until 3 to 7 days after reperfusion. Conclusions Rapid induction of VEGF gene expressio n after transient MCA occlusion was demonstrated at both mRNA and prot ein levels. Cortical neurons and pial cells were the source of VEGF pr oduction in this model, but the temporal profiles of the induction bet ween these cells were different. The early but dissociative induction of VEGF between neuronal and pial cells suggests different roles of th e protein in their cells after transient MCA occlusion.