Document Detail


The novel VEGF receptor antagonist, VGA1155, reduces edema, decreases infarct and improves neurological function after stroke in rats.
MedLine Citation:
PMID:  21063140     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
Vascular endothelial growth factor (VEGF) is a major mediator of angiogenesis and also a strong vascular permeability factor. Blockade of VEGF may have a potential to treat cerebral edema after brain injury. We evaluated the effect of VGA1155 (5- [N-Methyl-N-(4-octadecyloxyphenyl)acetyl]amino-2- methylthiobenzoic acid), a novel binding antagonist of VEGF, on cerebral edema after transient focal cerebral ischemia. Focal cerebral ischemia was induced with the suture occlusion method for 2 h. In the treatment group, a single dose of VGA1155 (1 ~ 50 mg/kg i.p.) was administrated 30 min before the induction of focal ischemia, and the vehicle group received phosphate buffer only. The brain water content, Evans blue extravasation, infarct volumes and neurological score were determined. Physiological parameters were not influenced by the administration of VGA1155. The brain water content at 24 h after cerebral ischemia was significantly reduced by intraperitoneal administration of VGA1155 and the dose of 10 mg/kg showed the maximum effect on brain water content (81.8 ± 0.5% in non treated group vs. 80.2 ± 0.6% in treated group). With this dose, VGA1155 also reduced vascular permeability from 2.2 ± 0.8 µg/g to 1.2 ± 0.5 µg/g studied at 6 h after the ischemia by intravenous injection of Evans blue. VGA1155 administration significantly reduced infarct volume and improved neurological scores at 1 week after ischemic injury. The data suggested that VGA1155 has antiedematous effect in acute phase after transient focal cerebral ischemia and improves neurological and histological outcomes 1 week after ischemic injury.
Authors:
Junji Koyama; Shigeru Miyake; Takashi Sasayama; Yoshiyuki Chiba; Takeshi Kondoh; Eiji Kohmura
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-08-19
Journal Detail:
Title:  The Kobe journal of medical sciences     Volume:  56     ISSN:  1883-0498     ISO Abbreviation:  Kobe J Med Sci     Publication Date:  2010  
Date Detail:
Created Date:  2010-11-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0413531     Medline TA:  Kobe J Med Sci     Country:  Japan    
Other Details:
Languages:  eng     Pagination:  E1-11     Citation Subset:  IM    
Affiliation:
Department of Neurosurgery, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan. jkoyama@hp.pref.hyogo.jp
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