2,3,4,5 Selective inhibitors of αvβ3 have been incompletely studied in animal models of brain ischemia. 1 With ischemic injury to the brain, integrin αvβ3 is selectively upregulated whereas many others are downregulated.
Recent attention has turned to inhibition of intercellular adhesion molecules for treatment of ischemic stroke. Western blotting showed reduction of phosphorylated Flk-1 (a vascular endothelial growth factor receptor), reduction of phosphorylated FAK (an intracellular kinase phosphorylated in the presence of VEGF), reduction of VEGF, and reduction of fibrinogen in the cRGDfV treatment group.Ĭonclusions- The selective integrin αvβ3 inhibitor cRGDfV improves outcomes in the MCAO model by preserving the blood-brain barrier, which mechanistically may occur in a VEGF- and VEGF-receptor–dependent manner. Results- Treatment with cRGDfV reduced infarction, reduced brain edema, reduced exudation of Evans blue and IgG, and prevented fibrinogen deposition. Physiological parameters, expression of integrin αvβ3, infarction volume, brain water content, Evans Blue exudation, IgG exudation, histology, immunohistochemistry, and western blotting were studied in 4 groups of animals: sham operation (n=13), untreated (n=18), nonfunctioning peptide treatment (n=19), and cRGDfV treatment (n=27). Methods- Rats were treated before and after MCAO with cRGDfV. We studied selective inhibition of integrin αvβ3 with cyclo (cRGDfV) in the rat middle cerebral artery occlusion model (MCAO). Customer Service and Ordering Informationīackground and Purpose- Recent studies have shown that selective inhibition of specific subsets of intercellular adhesion molecules protects the brain during ischemia.
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