Focal cerebral ischemia in rodents and ischemic stroke in humans induce expression of vascular endothelial growth factor (VEGF), a major promoter of vascular permeability (VP) leading to brain edema and potential deterioration of clinical outcome. We have shown that a novel Src kinase inhibitor (Golas et al., Cancer Res. 2003, 63:375) provides effective neuroprotection from ischemic injury induced by a transient occlusion of the middle cerebral artery (tMCAO) when administered as a single i.v. bolus at 30 min post-MCAO (Zaleska et al., SFN 2003). The goal of the current study was to evaluate the therapeutic window for Src inhibition by SKI-606. Wistar rats subjected to a 90 min tMCAO using an intraluminal suture approach were treated with a single bolus dose of 10 mg/kg of SKI-606 administered i.v. at 0.5, 1.5, 3, 4, 5, or 6 hours post-MCAO. Neurological deficits and body weight loss/gain were evaluated over the course of 48 hours. Infarct volumes were assessed by TTC staining. A single dose treatment with...