Björn Gustavii

Chapter 83 Neural transplantation in Parkinson's disease: the Swedish experience

Publisher Summary This chapter discusses the neural transplantation in Parkinsons disease (PD). The fetal nigral implants have provided a modest improvement in motor function in PD patients. This is consistent with the presence of small surviving grafts indicated by positron emission tomography (PET). Despite the lack of a therapeutically significant improvement in these patients, results together with the solid animal experimental data obtained with DA neuron grafting both in rodents and in non-human primates provide a strong rationale to pursue this approach. However, widespread clinical trials with neural transplantation in PD are probably not warranted at this time. From the observations made on the 2 patients reported in the chapter, the following conclusions are drawn: (1) ventral mesencephalic tissue obtained from routine elective abortions can be implanted into the brains of immunosuppressed PD patients without major complications; (2) no major graft-induced improvement of therapeutic value to the patients has been observed; (3) neurophysiological methods and the clinical test battery have detected significant but small post-operative improvements that could indicate a graft effect; and (4) PET provides an evidence of a slight increase of 18 F-dopa uptake in the transplanted striatum, suggesting that small grafts have survived.

Extensive efferent projections of intra-striatally transplanted striatal neurons as revealed by a species-specific neurofilament marker and anterograde axonal tracing.

Publisher Summary The human neurofilaments (HNF) antibody reveals a remarkably extensive graft-to-host projection from the human fetal striatal tissue grafts. As revealed by the Phaseolus vulgaris leucoagglutinin (PHA-L) experiment described in the chapter, the axons growing out from the striatal grafts to the globus pallidus were myelinated and formed the normal types of symmetrical synapses with the host pallidal neurons. In contrast to the monoaminergic types of neurons, which have been seen to grow preferentially within grey matter to reach distant target sites, the axons of the striatal neurons grew within white matter pathways, such as the internal capsule, the pyramidal tract, and the corpus callosum. Indeed, both in the PHAL labeled rat-to-rat grafts and the HNF labeled human-to-rat grafts, the labeled axons ran intermingled with the host myelinated fibers, both within and on the surface of the myelinated fiber bundles. Within the internal capsule and the cerebral peduncle, the HNF labeled axons formed a well-defined bundle that occupied a position very similar to that of the striato-nigral pathway and the cortico-ponto-spinal axons. Axons appeared to branch off from this descending bundle specifically into those nuclei that normally receive prominent projections from either the striato-fugal or the cortico-fugal axonal pathways—that is, the globus pallidus, the subthalamic nucleus, the substantia nigra pars reticulate, and the pontine nuclei. This indicates a remarkable precision in the ability of the outgrowing axons to find their way over extended distances, up to about 10 mm to reach the pontine nuclei and about 20 mm for the most advanced axons to reach the cervical spinal cord.