The role of vascular endothelial growth factor in angiogenesis and cerebral edema formation in rat following gamma knife surgery

【作者】 魏铭； 李宏； 黄惠玲； 徐德生； 只达石； 刘东； 张宜培；

【Author】 Ming Wei,Hong Li,Huiling Huang,DeshengXu,Dashi Zhi,Dong Liu,Yipei Zhang

【机构】 天津医科大学第二医院神经外科； 天津市神经外科研究所；

【摘要】 <正>Objective Formation of cerebral edema after gamma knife surgery(GKS) is in part associated with the pathological angiogenesis.However,the molecular mechanisms underlying these phenomena are not fully understood.Vascular endothelial growth factor(VEGF) is the possible factor involved in pathological angiogenesis.In this study,we analyzed temporal changes in VEGF expression in cerebral cortex after GKS in rat and effect of VEGF on angiogenesis and cerebral edema.Methods Adult male wistar rats were subjected to GKS.Maximum dosages of 60 Gy were given at the isocenter of the radiation using a 4 - mm collimator.Animals were sacrificed at 4,8,12,16,20,and 24 weeks after GKS. The vessel density was measured by CD31~+ cell count,and vascular structures were studied using light and electron microscopy.Immunohistochemistry,ELISA and semiquantitative RT - PCR analysis were employed for VEGF.Brain water content was measured by the wet and dry weight method.The BBB permeability was evaluated by EB extravasation experiment.Results In the irradiated tissues,there was a decrease of vessel at 4 weeks,but this initial change is transient and followed by more intense vessel density 8 - to 20 - weeks later,and the vascular damage was also observed at 20 weeks.Following GKS early,VEGF was expressed at a relatively low level,whereas there was a progressive increase in VEGF expression in cortex on the ipsilateral side to the radiation injury 12 weeks after GKS.Maximal levels of VEGF expression were observed at 16 week after GKS and then they gradually decreased at 20 and 24 weeks.These immunohistochemical findings were confirmed by ELISA and RT - PCR.Current studies also demonstrated a opening of the blood brain barrier (BBB) and a increase of brain water content at same period.Conclusion The time - course of changes in VEGF expression observed in the present study correlates with the disruption of the BBB suggesting that VEGF plays a pivotal role in promoting the formation of vasogenic edema in GKS.更多还原

【Abstract】 Objective Formation of cerebral edema after gamma knife surgery(GKS) is in part associated with the pathological angiogenesis.However,the molecular mechanisms underlying these phenomena are not fully understood.Vascular endothelial growth factor(VEGF) is the possible factor involved in pathological angiogenesis.In this study,we analyzed temporal changes in VEGF expression in cerebral cortex after GKS in rat and effect of VEGF on angiogenesis and cerebral edema.Methods Adult male wistar rats were subjected to GKS.Maximum dosages of 60 Gy were given at the isocenter of the radiation using a 4 - mm collimator.Animals were sacrificed at 4,8,12,16,20,and 24 weeks after GKS. The vessel density was measured by CD31~+ cell count,and vascular structures were studied using light and electron microscopy.Immunohistochemistry,ELISA and semiquantitative RT - PCR analysis were employed for VEGF.Brain water content was measured by the wet and dry weight method.The BBB permeability was evaluated by EB extravasation experiment.Results In the irradiated tissues,there was a decrease of vessel at 4 weeks,but this initial change is transient and followed by more intense vessel density 8 - to 20 - weeks later,and the vascular damage was also observed at 20 weeks.Following GKS early,VEGF was expressed at a relatively low level,whereas there was a progressive increase in VEGF expression in cortex on the ipsilateral side to the radiation injury 12 weeks after GKS.Maximal levels of VEGF expression were observed at 16 week after GKS and then they gradually decreased at 20 and 24 weeks.These immunohistochemical findings were confirmed by ELISA and RT - PCR.Current studies also demonstrated a opening of the blood brain barrier (BBB) and a increase of brain water content at same period.Conclusion The time - course of changes in VEGF expression observed in the present study correlates with the disruption of the BBB suggesting that VEGF plays a pivotal role in promoting the formation of vasogenic edema in GKS.更多还原