Vascular endothelial growth factor antagonist reduces brain edema formation and venous infarction.
OBJECTIVE
Cerebral venous ischemia often induces severe brain edema. Vascular endothelial growth factor (VEGF), which induces angiogenesis, is also known as vascular permeability (VP) factor. The present study was undertaken to investigate whether the inhibition of VEGF could reduce brain edema formation and cerebral venous infarction (CVI) in a rat 2-vein occlusion (2-VO) model.


METHODS
We used 2-VO model in which 2 adjacent cortical veins were photochemically occluded. Male Wistar rats (n=25) were divided into 2 groups: one group was treated with a VEGF antagonist (antagonist group, n=10) and the second group was treated with phosphate-buffered solution (PBS) (PBS group, n=15). VEGF antagonist or PBS was injected intraperitoneally immediately after 2-VO. The developing ischemic infarct was evaluated by magnetic resonance imaging (MRI) and histology 24 hours after occlusion.


RESULTS
VEGF expression was observed in the cytoplasm of neurons exclusively in the area of vasogenic edema that was shown as a high-intensity area in the apparent diffusion coefficient of water map. Ischemic volumes calculated from each MR images, which are related to infarction and/or vasogenic edema, respectively, were significantly smaller in the antagonist group as compared with the PBS group (P<0.05)


CONCLUSIONS
Our study is the first to provide evidence that the inhibition of VEGF attenuates VP and reduces CVI in the acute stage. Although VEGF is a significant angiogenesis factor, we concluded that the inhibition of VEGF might be a new therapy for both brain edema formation and CVI.
Kimura
R
R
Department of Neurosurgery, Nara Medical University, Kashihara, 634, Nara, Japan. nakasehi@nmu-gw.naramed-u.ac.jp
Nakase
H
H
Tamaki
R
R
Sakaki
T
T
D000818:Animals; D001921:Brain / Q000473:pathology*; D020520:Brain Infarction / Q000188:drug therapy*; D002545:Brain Ischemia / Q000473:pathology; D002544:Cerebral Infarction; D003593:Cytoplasm / Q000378:metabolism; D004487:Edema / Q000188:drug therapy*; D007150:Immunohistochemistry; D007511:Ischemia / Q000188:drug therapy / Q000473:pathology; D008027:Light; D008279:Magnetic Resonance Imaging; D008297:Male; D018919:Neovascularization, Physiologic; D009474:Neurons / Q000378:metabolism; D010710:Phosphates / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013927:Thrombosis; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000378:metabolism
D010710:Phosphates; D042461:Vascular Endothelial Growth Factor A