To determine the role of extracellular matrix molecules and their integrin ligands in CNS remyelination, we have examined in experimentally induced focal demyelinated lesions the expression of the two classes of integrins implicated in oligodendrocyte development and myelination: alpha 6 laminin-binding integrins and alpha V integrins that bind a range of extracellular matrix proteins containing the -Arg-Gly-Asp- (RGD) recognition sequence. Only alpha V integrins were up-regulated during remyelination, being expressed on oligodendrocyte precursor cells during their recruitment into the lesion. Next, therefore, we examined the expression of extracellular matrix ligands for alpha V integrins and documented increased expression of tenascin-C, tenascin-R, fibronectin, and vitronectin. Taken together with our previous discovery of high levels of expression of another alpha V ligand, osteopontin, during remyelination in these lesions, our findings suggest that alpha V integrins make an important contribution to successful repair in the CNS. (C) 2009 Wiley-Liss, Inc.