IMPROVED MOTOR FUNCTION OF DENERVATED RAT HINDLIMB MUSCLES INDUCED BYEMBRYONIC SPINAL-CORD GRAFTS

Loss of motoneurons results in a decrease in force production by skele tal muscles and paralysis. Although it has been shown that missing mot oneurons of rats can be replaced by embryonic homotopic neurons, attem pts to guide their axons to their target muscles that have lost their innervation have been unsuccessful. In this study attempts were made t o guide axons from grafted embryonic motoneurons to their target via a reimplanted ventral root. Adult hosts that received an embryonic graf t prelabelled with 5-bromo-2'-deoxyuridine had their L4 ventral root a vulsed and reimplanted into the spinal cord. Three to six months later , neurons that had their axons in the L4 ventral ramus were retrograde ly labelled with fast blue and diamidino yellow. in five animals that had received an embryonic graft 116 +/- 16 cells were retrogradely lab elled, and of these at least 15% were of graft origin, since they were positive for 5-bromo-2'-deoxyuridine. In five animals that had their L4 ventral root reimplanted but did not receive a graft, only 12 +/- 1 .3 cells were retrogradely labelled. However, meaningful functional re covery could be achieved only if the regenerating axons of embryonic m otoneurons found in the L4 ventral ramus were able to reverse the loss of force of muscles that had lost their innervation. This study shows that axons of embryonic motoneurons grafted into an adult rat spinal cord, as well as some axons of host origin, can be guided to denervate d hindlimb muscles via reimplanted lumbar ventral roots. In normal rat s similar to 30 motor axons innervated the extensor digitorum longus a nd 60 innervated the tibialis anterior via the L4 ventral root. In rat s that did not receive a graft only 3.7 +/- 1.2 axons reached the exte nsor digitorum longus and 3.5 +/- 0.4 reached the tibialis anterior mu scle via the implanted L4 ventral root. In animals that had an embryon ic graft, 7.6 +/- 0.5 axons innervated the extensor digitorum longus a nd 8.5 +/- 0.5 reached the tibialis anterior muscle via the implanted root. In rats without a transplant the maximum tetanic tension elicite d by stimulating the implanted L4 root was 16 +/- 7 g for the extensor digitorum longus and 53 +/- 36 g for the tibialis anterior muscle, wh ereas the corresponding muscles in animals that had an embryonic graft developed 82 +/- 16 and 281 +/- 95 g respectively. Thus it appears th at the grafted motoneurons contributed to the innervation and function al recovery of the denervated muscles.