title: Post-ischemic administration of vascular endothelial growth factor inhibitor in a rat model of cerebral venous infarction.
abstract: Cerebral venous ischemia can result in severe brain edema. Inhibition of vascular endothelial growth factor (VEGF) activity by a neutralizing antibody can completely block the hypoxia-induced increase in vascular permeability. VEGF, which induces angiogenesis, also acts as a vascular permeability (VP) factor. We previously showed that inhibition of VEGF attenuates VP and reduces cerebral venous infarction (CVI) in the acute stage. The present study investigated the therapeutic time window during which inhibition of VEGF can reduce CVI in a rat two-vein occlusion (2-VO) model. A 2-VO model was created by photochemically occluding two adjacent cortical veins. Male Wistar rats (n = 42) were assigned to one of four groups: Group 1 was treated with a VEGF antagonist at 24 hours after 2-VO (n = 11); Group 2 was treated with phosphate-buffered solution (PBS) at 24 hours after 2-VO (n = 11); Group 3 was treated with a VEGF antagonist at 48 hours after 2-VO (n = 10); and Group 4 was treated with PBS at 48 hours after 2-VO (n = 10). The developing ischemic infarct was evaluated histologically at 7 days after 2-VO. CVI areas were significantly smaller in Group 1 than in Groups 2, 3, and 4 (p <0.05) but were similar when comparing Groups 3 and 4. Anti-VEGF therapy was effective in reducing CVI in rats if started within 24 hours after 2-VO.
authors.affiliation: Department of Neurosurgery, Nara Medical University, Kashihara, Nara, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Miyake
authors.forename: Ichiro
authors.initials: I
authors.lastname: Nakagawa
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Takeshima
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Nishimura
authors.forename: Young-Su
authors.initials: YS
authors.lastname: Park
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Nakamura
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakase
mesh_terms: D000818:Animals; D002544:Cerebral Infarction / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D002550:Cerebral Veins; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage* / Q000037:antagonists & inhibitors*
chemical_list: D042461:Vascular Endothelial Growth Factor A