Background and Purpose-Recent studies have shown that selective inhibition of specific subsets of intercellular adhesion molecules protects the brain during ischemia. We studied selective inhibition of integrin ␣v3 with cyclo [Arg-GlyAsp-D-Phe-Val] (cRGDfV) in the rat middle cerebral artery occlusion model (MCAO). Methods-Rats were treated before and after MCAO with cRGDfV. Physiological parameters, expression of integrin ␣v3, infarction volume, brain water content, Evans Blue exudation, IgG exudation, histology, immunohistochemistry, and western blotting were studied in 4 groups of animals: sham operation (nϭ13), untreated (nϭ18), nonfunctioning peptide treatment (nϭ19), and cRGDfV treatment (nϭ27). Results-Treatment with cRGDfV reduced infarction, reduced brain edema, reduced exudation of Evans blue and IgG, and prevented fibrinogen deposition. Western blotting showed reduction of phosphorylated Flk-1 (a vascular endothelial growth factor [VEGF] 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. Conclusions-The selective integrin ␣v3 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. (Stroke.
We found a trend toward a lesser incidence of DINDs and a lesser incidence of poor outcome caused by cerebral vasospasm in edaravone-treated patients. It might therefore be suggested that edaravone is a useful agent for the treatment of aneurysmal SAH.
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