Alterations in the expression of vascular endothelial growth factor in the rat brain following gamma knife surgery

Cheng,Lei; Ma,Lin; Ren,Hecheng; Zhao,Hongwei; Pang,Yiqiang; Wang,Yongheng; Wei,Ming

doi:10.3892/mmr.2014.2520

Alterations in the expression of vascular endothelial growth factor in the rat brain following gamma knife surgery

Authors:
- Lei Cheng
- Lin Ma
- Hecheng Ren
- Hongwei Zhao
- Yiqiang Pang
- Yongheng Wang
- Ming Wei
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Affiliations: Department of Neurosurgery, Tianjin Huanhu Hospital, Tianjin 300060, P.R. China, Department of Neurosurgery, Jixian People's Hospital, Tianjin 301900, P.R. China, Department of Neurosurgery, Fourth Hospital of Baotou, Baotou, Inner Mongolia 014030, P.R. China, Department of Neurosurgery, First Hospital of Qinhuangdao, Qinhuangdao, Hebei 066000, P.R. China, Department of Neurosurgery, Second Hospital of Tianjin Medical University, Tianjin 300211, P.R. China
Published online on: August 27, 2014 https://doi.org/10.3892/mmr.2014.2520
Pages: 2263-2270
Copyright: © Cheng et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Gamma knife surgery (GKS) is used for the treatment of various brain diseases. However, the mechanisms underlying brain injury following irradiation remain to be elucidated. Given that vascular endothelial growth factor (VEGF) is closely associated with pathological angiogenesis and the permeability of the blood brain barrier (BBB), the present study was designed to analyze temporal alterations in VEGF expression in the cerebral cortex and the effect of VEGF on cerebral edema in rats following GKS. Adult male Wistar rats were subjected to GKS at maximum doses of 60 Gy. Animals were sacrificed between 4 and 24 weeks after GKS. Immunohistochemistry, enzyme‑linked immunosorbent assay and reverse transcription‑polymerase chain reaction (RT‑PCR) were employed for detecting VEGF expression. The vessel density was measured by CD31+ cell count and vascular structures were examined using electron microscopy. Brain water content and BBB permeability were measured in the present study. VEGF expression in the irradiated cortex progressively increased until 16 weeks after GKS when the maximal expression was reached, and then gradually decreased to the control level 24 weeks after GKS. These findings were confirmed by RT‑PCR. A mild decrease in vessel density was observed 4 weeks after GKS, followed by an increase in vessel density between 8 and 20 weeks later. Furthermore, previous studies also demonstrated vascular damage, opening of the BBB and an increase in brain water content occurring simultaneously. To the best of our knowledge, these data demonstrated for the first time dynamic changes in VEGF expression following GKS and also suggest the importance of VEGF expression in pathological angiogenesis and edema formation following GKS.

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