The regenerative response of adult rat CNS neurons to the implantation of peripheral nerve grafts into the corpus striatum

The study was focused on responses of CNS neurons in adult rats to autologous tibial nerve grafts implanted into the striatum, an area of particular interest due to its heterogeneity of cell content and clinical importance. Transmission electron microscopy identified many small non-myelinated axonal profiles, presumptive regenerating CNS axons, in the brain surrounding the graft. Similar axonal profiles also invaded living, but not freeze-killed, peripheral nerve grafts implanted into the striatum and retrograde labelling with HRP-conjugated ligands showed that the majority of regenerating axons originated from neurons in the substantia nigra pars compacta. Comparatively few striatal neurons, which showed some morphological similarities, were retrogradely labelled, perhaps indicating the preferential regeneration of particular populations. Many retrogradely labelled neurons were found within the ventral pallidum and the area close to the medial forebrain bundle but only if the graft tip terminated within these regions. Peripheral nerve grafts contained much higher levels of NGF than intact striatal tissue, but, although striatal NGF levels increased slightly after graft implantation, no concurrent up-regulation of the low affinity NGF receptor (p75LNGFR) was detected in any striatal neurons, even those known to be NGF-sensitive. Two populations of striatal interneurons underwent perikaryal enlargement after the implantation of living, but not freeze-killed, grafts demonstrating that this response was mediated by factors produced by living grafts, and regenerating axons which appeared to originate from both these populations of striatal neurons were identified within the grafts as early as two weeks post operation. Additionally, a small set of large striatal perikarya was found to express mRNA for GAP-43 and the cell adhesion molecule L1, even in the control striatum; graft implantation had no apparent effect on their expression of either molecule. Similarly, neurons of the substantia nigra pars compacta, which most successfully regenerated long axons into the graft, contained high levels of these molecules irrespective of the presence of a nerve graft in the striatum