The disclosed invention relates to the use of perlecan domain V (DV) for the treatment of stroke, traumatic brain injury (TBI) or spinal cord injuries (SCI). In certain embodiments, fusion proteins of DV can be used for the treatment of stroke, TBI or SCI. DV is also referred to as endorepellin in the art. This application also provides compositions and combination therapies for the treatment of stroke, TCI and/or SCI. Another aspect of the invention provides methods of restoring motor function in subjects having neurological damage arising from a stroke, TBI or SCI.