Induction of platelet derived-endothelial cell growth factor in the brain after ischemia.

ABSTRACT

OBJECTIVES: Platelet derived-endothelial cell growth factor (PD-ECGF) is a highly potent angiogenic factor. Although angiogenesis plays an active role in pathophysiology of stroke, the expression pattern of this molecule in ischemic brain has not been investigated. In the present study, therefore, we investigated the change of PD-ECGF expression in the brain after ischemia. METHODS: Using male Wistar rats, the right middle cerebral artery was occluded by a nylon thread for 90 minutes. The animals were decapitated 3 hours, 1, 4 and 10 days after the reperfusion, and frozen sections were prepared. We then performed immunohistochemistry for PD-ECGF and identified the cell phenotype which strongly expressed it by fluorescent double staining. RESULTS: In the sham-operated brain, only small numbers of cells slightly expressed PD-ECGF. The number of positively stained cells increased at the peri-ischemic area from hour 3 of reperfusion. Not only small-sized cells but also large-sized cells became stained. The number of stained cells further increased, and peaked at day 4 for large-sized cells and at day 10 as to small-sized cells. Fluorescent double staining revealed that both large-sized and small-sized cells were neurons, indicating that neurons are the main source of PD-ECGF production in the ischemic brain. DISCUSSION: PD-ECGF has a strong angiogenic property without vascular permeability increasing effect. This molecule may have a therapeutic potential for ischemic stroke treatment.