We have shown (Zaleska et al., SFN 2003 and Gonzales et al., SFN, 2003) that a suppression of Src kinase activity within several hours following a transient occlusion of the middle cerebral artery (tMCAO) reduces brain injury and neurological deficits, and protects from post-stroke weight loss as evaluated after 48 hours of reperfusion. The goal for the current study was to investigate whether post-stroke inhibition of Src can provide a long-term neurological benefit. Wistar rats were subjected to a permanent occlusion of the middle cerebral artery by electrocauterization (pMCAO), a model of focal ischemic stroke resulting in infarction in the sensorimotor cortex of the MCA territory. SKI-606, a potent novel Src kinase inhibitor (Golas et al., Cancer Res. 2003, 63:375) or vehicle was administered at 1.5, 4, 24 and 48 hours post-MCAO at 10 mg/kg i.v. Animals were evaluated in a postural test, visual and tactile forelimb foot placement and hindlimb placement tests (maximum neurological deficit score = 12) on...