Abstract: Compositions and methods for modulating neural outgrowth, including treating neural damage, via the major histocompatibility complex I (“MHC I”) molecule. Methods for identifying agents that reduce MHC I-induced inhibition of neurite outgrowth. Methods for promoting neural outgrowth comprising administering MHC I molecules (native, recombinant, or those encoded by gene fusion) or biologically-active fragments thereof. Pharmaceutical compositions comprising vectors comprising nucleic acid sequences encoding MHC I in operable linkage with a promoter and a pharmaceutically-acceptable carrier or diluent. Small interfering RNA (“siRNA”) that down-regulates expression of an MHC I gene.