tPA induces Akt phosphorylation via a plasminogen-independent mechanism. (A,B) Representative Western blot analysis of pAkt and total Akt in brain extracts from Plg^−/− mice (A) and tPA^−/− animals (B) 1 hour after MCAO. A subset of tPA^−/− mice was either left untreated (NT) or injected directly into the ischemic tissue with murine tPA (tPA) or a combination of tPA and RAP (tPA + RAP). S denotes sham-operated animal. Each observation was repeated 3 times.