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Motoneuron survival and axon regeneration following immediate versus delayed implantation of peripheral nerve graft into the spinal cord of adult rats with c5 and c6 root avulsion Tarazi, Christine

Abstract

Avulsion of spinal nerve roots is a CNS injury that results in motoneuron cell death and paralysis of the affected limb. It has been demonstrated in rats, cats and primates that following spinal nerve root avulsion injured motoneurons can extend axons into ventral roots or peripheral nerve (PN) grafts that have been immediately reimplanted into the spinal cord and result in functional reinnervation of denervated muscles. The effects of delayed PN graft implantation on motoneuron survival and axonal regeneration has not been studied in animals. Following avulsion of the left C5 and C6 ventral and dorsal roots in adult rats, the free end of a 3.5cm segment of common peroneal nerve was implanted into the ventrolateral area of the cord at C5 and C6. There were five groups of animals based on the time interval between root avulsion and PN graft implantation: immediate implantation, 1 week, 1 month, 2 months and 6 months. Two months after PN implantation, a fluorescent axonal tracer, Rhodamine-Dextran amine (RDA) was applied to the free end of the graft. Counts of RDA labeled neurons in the ipsilateral ventral horn were compared among the groups. Using the cell counts in the immediate implantation group (mean of 761 cells = 100%) as a reference for comparison, counts of RDA-labeled neurons was 82% at 1 week, 44% at 1 month and 38% at both 2 and 6 months. Counts were significantly lower in the 1, 2 and 6-month groups. To allow identification of C5 and C6 motoneurons, a separate group of experiments were done in which C5 and C6 motoneurons were labeled with another axonal tracer Fluorogold (FG) prior to avulsion, and PN grafts were implanted either immediately, 10 days or 1 month after root avulsion. Counts of FG, RDA or double-labeled neurons revealed that the % of ventral horn neurons that are G5 or C6 motoneurons are 31% (immediate), 33% (10 day) and 6% (1 month). A delay of 1 month in PN graft implantation resulted in a significant decrease in 1) the number of surviving C5 and C6 motoneurons; 2) the proportion of surviving C5 and C6 motoneurons that regenerated axons into the graft.

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