Fetal spinal cord transplants rescue some axotomized rubrospinal neurons from retrograde cell death in adult rats.

Intraspinal transplants of fetal spinal cord may contribute to recovery after spinal cord injury by keeping axotomized neurons alive. In this study we examined whether transplants rescued axotomized red nucleus (RN) neurons from retrograde cell death in adult rats. RN neurons were labeled by retrograde transport of Fluorogold (FG); 1 week later right-sided RN neurons were axotomized by left-sided hemisection at C3-4 vertebral level, and Embryonic Day 14 spinal cord or gelfoam was introduced into the cavity. Additional rats received hemisection and a transplant of fetal spinal cord or gelfoam without FG injection. At 2 and 4 months, the number of neurons in the magnocellular portion of the RN contralateral to the hemisection decreased 35-40% in rats that received gelfoam; mean soma area of surviving neurons decreased 40%. RN cell loss was reduced to 20% in rats that received fetal spinal cord transplants, but the decrease in mean soma area was unchanged. Transplants therefore rescued about half of the axotomized RN neurons that otherwise would have died but did not prevent perikaryal atrophy. Anterograde transport of WGA-HRP injected into RN 2 months after transplantation showed that rubrospinal axons reached the site of injury but rarely entered transplants; FG injections caudal to transplants showed that axons of transplant neurons extended at least two segments into host spinal cord. Fetal spinal cord transplants may therefore contribute to locomotor recovery in adults with spinal cord injuries both by preventing retrograde cell death and by establishing novel circuits across the site of injury.