Observations on the development of transplanted embryonic ventral horn neurones grafted into adult rat spinal cord and connected to skeletal muscle implants via a peripheral nerve.

Embryonic spinal cord grafts from 12-day-old rat embryos were placed into the lumbar spinal cord of adult rats depleted of sciatic motoneurones by a neonatal nerve injury. A soleus muscle was removed from the leg and implanted paravertebrally, the proximal end of its nerve connected to the graft site. Fluorescent retrograde tracers injected into the soleus implant, 37-64 days postoperatively, labelled neurones that had grown axons to the muscle. Approximately one-fifth of retrogradely labelled neurons were within the graft; however, the majority were found within the host spinal cord close to the graft. These included large neurons within the motoneurone-depleted dorsolateral ventral horn. In control experiments a muscle and nerve were implanted but no embryonic tissue grafted. Significantly fewer neurones were labelled. In some animals, one tracer was injected into the soleus muscle whilst another was applied to the cut sciatic nerve ipsilateral to the graft site. No neurones were found to project axons to both targets. In animals that received grafts prelabelled with bromodeoxyuridine (BrDU) some neurones were found to be both BrDU positive and retrogradely labelled from the soleus implant. These were most frequently within the motoneuron-depleted ventral horn ipsilateral to the graft. Thus, grafted neurones may migrate to an appropriate location within the host neuropil. Acetylcholinesterase (AChE) histochemistry showed the graft site contained immature but AChE-positive neurones. Some regions of host ventral horn contained unusually few AChE-positive nerve fibres and occasional large AChE-positive neurones, some of which were also retrogradely labelled from the implanted muscle. Studies of implanted soleus 21-90 days after transplantation showed that muscle fibres, after initial degeneration, regenerated displaying differing phenotypes, presumably under the influence of new motor innervation.