Regeneration of adult mammalian CNS is poor as a result of environmental factors that prevent axon growth. The major factors hampering regeneration of central axons include proteins released from the damaged myelin sheets of the injured neuronal pathways and formation of the glial scar. By using an experimental model of human CNS injury, we show that survival and neurite outgrowth of human central neurons are significantly enhanced by the soluble KDI domain of γ1 laminin. Our results indicate that the KDI domain appears to neutralize both glia-derived inhibitory signals and inhibitory molecules released from the myelin of the adult human spinal cord. We propose that the KDI domain may enhance regeneration of injuries in the adult mammalian CNS. © 2003 Wiley-Liss, Inc.