Effect of glucocorticoid on expression of vascular endothelial growth factor, FLT-1 and FLK-1 after gamma knife surgery in rats

Abstract

Objective To investigate the effect of methylprednisolone (MP) on the expression of vascular endothelial growth factor (VEGF) and its receptors in rats after gamma knife surgery (GKS),and elucidate the mechanism of the unique benecial effect of glucocorticoid therapy on brain edema after GKS.Methods Male Wistar rats were subjected to GKS and given MP (5-30 mg/kg body weight) 12 weeks after GKS.Blood-brain barrier permeability and brain water content were detected at 12th and 13th week after irradiation.The protein and mRNA expression of VEGF and its receptors was determined by using immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR).Results The brain water content and EB extravasations were significantly reduced in MP-treated rats as compared with the controls.High dose MP downregulated the protein expression of VEGF ( 12.40 ±0.88 cells/high power field vs.30.20 ± 1.20 cells/high power field),but upregulated the protein expression of Flt-1 ( 25.40 ± 0.86vs.11.80 ± 0.50) as compared with the controls.The relative level of VEGF mRNA in high dose MP group was 70％ of the controls,whereas the level of Flt-1 mRNA significantly increased,showing a 1.8 fold difference.Conclusion Glucocorticoid therapy for brain edema induced by GKS is associated with differential regulation of VEGF and its receptors. Key words: Brain edema; Radiosurgery; Vascular endothelial growth factor