Among the most promising therapeutic strategies to facilitate axonal regeneration after spinal cord injury is the transplantation of various cellular substrates into the injury site. With the establishment of a glial scar and cyst at the injury site over time, the implantation of such cells in the chronic injury setting may require some resection of these nonpermissive elements, which could concomitantly reinjure already severed axons. This study evaluates the response of chronically injured rubrospinal neurons to such a second axotomy. Our findings indicate that the second axotomy does not lead to an accelerated loss of rubrospinal neurons, which represents an important finding for those who evaluate axonal regeneration of this motor system in chronic transplantation studies. (C) 2002 Elsevier Science (USA).