Delayed implantation of a peripheral nerve graft reduces motoneuron survival but does not affect regeneration following spinal root avulsion in adult rats

Abstract

Adult spinal motoneurons can regenerate their axons into a peripheral nerve (PN) graft following root avulsion injury if the graft is implanted immediately after the lesion is induced. The present study was designed to determine how avulsed motoneurons respond to a PN graft if implantation takes place a few days to a few weeks later. Survival, regeneration, and gene expression changes of injured motoneurons after delayed PN graft implantation were studied. The survival rates of spinal motoneurons were 78%, 65%, 57%, or 53% if a PN graft was implanted immediately, 1, 2, or 3 weeks after root avulsion, respectively. Interestingly, most of the surviving motoneurons were able to regenerate their axons into the graft regardless of the delay. All regenerating motoneurons expressed p75, but not nNOS, while all motoneurons that failed to regenerate expressed nNOS, but not p75. p75 and nNOS may, therefore, be used as markers for success or failure to regenerate axons. In the group with immediate graft implantation, 85% of the surviving motoneurons extended axons into the PN graft, while in the groups in which implantation was delayed 1, 2, or 3 weeks, 84%, 82%, and 83% of the surviving motoneurons, respectively, were found to have regenerated into the grafts. These findings indicate that avulsed spinal motoneurons retain the ability to regenerate for at least 3 weeks, and perhaps for as long as they survive. Therefore, the delayed implantation of a PN graft after root avulsion may provide a continued conducive environment to support regeneration.