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.

Nitric oxide synthase inhibitor attenuates number of regenerating spinal motoneurons in adult rats

“…1a-c). We compared the labeled motoneurons with the expression of p75 NTR , which is correlated with regenerating motoneurons as shown in our previous study [15]. Most of the regenerating motoneurons (labeled by fluorescent dye) were p75 NTR positive ( Fig.…”

P75 Nerve Growth Factor Receptor Is Expressed in Regenerating Human Nerve Grafts

“…Hence, the authors suggest that NGFRp75 could be a marker of ongoing axonal regeneration [22]. Our results imply that high expression of NGFRp75 in nerve grafts at the time of muscle transfer is favorable for the regeneration process, but further studies are needed in this field.…”

“…Expression is also increased in, e.g., mechanical trauma, focal ischemia, stroke, epileptic seizures, and Alzheimer's disease [18]. p75NGFR is also markedly increased in axotomized motoneurons [19 -21], or after spinal root avulsion [22], but the function of this receptor in normal adult motoneurons remains unknown [18,23]. It has also been suggested that p75NGFR participates in apoptosis of motoneurons and Schwann cells [11,18,23,24].…”

Repair and regeneration of lumbosacral nerve defects in rats with chitosan conduits containing bone marrow mesenchymal stem cells

“…However, it takes several weeks for the spinal motor neurons to regenerate their axons into the defects and reinnervate the target muscle. The distance between the neuron body and injury site will cause death of the motor neurons in the anterior horn of the spinal cord after lumbosacral nerve injury, which might be caused by lack of neurotrophic factors secreted by Schwann cells and target muscle [34,35]. Therefore, the neurotrophic factors secreted by BMSCs and chitosan conduit provide an appropriate micro environment for axotomised neurons to reach the target muscle.…”