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Adeno-associated virus vectors (type2) containing the marker gene--green fluorescent protein (AAV2-GFP) were used to transduce subventricular zone neural stem cells (NSCs). NSCs labelled by gene product--GFP were transplanted into adult Sprague-Dawley rat striatum. The animals were allowed to survive for 45 days, 90 days and 120 days before they were perfused. All the fixed brains were serially sectioned in the saggital plane,at the sickness of 30 microm with a cryostat microtome. These results showed that, at all stages, GFP labelled NSCs were seen in the injection sites,and a lot of them dispersed in the host brains. GFP labelled NSCs showed directional migration 45 days following transplantation. 120 days after transplantation, a group of GFP labelled NSCs migrated dorsally and posteriorly, reached corpus callosum; another group of transplanted NSCs migrated ventrally and posteriorly,reached substantia nigra, moreover,a number of these cells migrated through or over the substantia nigra and reached the more ventral boundary of the substantia nigra. The migrating NSCs were in chains, GFP labelled cells in substantia nigra were beta-tubulin III immunoreactive.

The rat model with a unilateral 6-OHDA-induced lesion of the dopaminergic system was used for experimental study on gene therapy for Parkinson's disease (PD). The plasmid pCMVTH (6.04 kb) was constructed as a vector containing the gene of tyrosine hydroxylase (TH) and transferred into cultured primary muscle cells by lipofection ex vivo. After expression of TH was determined in vitro, the intracerebral grafting (ICG) of these genetically modified cells was made in the striatum of PD rat model. The results showed that TH-expressing muscle cells had a long-term survival in the brain and induced a marked decrease in abnormal locomotion and increase in striatal dopamine levels for rat model.

The grafts of fetal substantia cell suspension grafts could bring into a behavioral effect and characteristics of histology and immunocytochemistry in rat models of PD after the grafts were transplanted either into the lateral ventricles or directly into the striatum. It was found that the intraparenchymal tromsplantation of fetal nigral cell suspensions not only was beneficial to reinnervation between host and grafts, but also produced more complete and steady effects than the intraventricular transplantation. We concluded that the restoration of nervous functional deficits of PD rats is likely to depend on both extensive dopaminergic reinnervation throughout the grafted sites and on closer integration of the grafts with the host striatal circuitry.

By using immunohistochemistry and Western blot, we observed the varied patterns of survival, development and growth of dopaminergic neurons after intrastriatal transplantation of fetal substantia nigra. There was a phenomenon of "developmental delay" of grafts in the host. As the time of transplantation went on, the grafted dopaminergic neurons could reinnervate the host neurons. The observation reveals that the reinnervation between graft and host is more beneficial to the functioning of the grafts.

The clinical application of brain transplantation for treating Parkinson's disease (PD) is limited because it is difficult to obtain ideal donor cells. In this study, the tyrosine hydroxylase (TH) gene was introduced into NIH-3T3 cell line and the genetically modified cells reacted positively with TH antiserum and released L-dopa. These cells were implanted into the striatum of PD rats. 3,6,9,12 days after implantation, the average rate of the abnormal rotational behavior recovery was 52.6%, 68.4%, 63.2%, 44.7%, respectively. This result is considered to be potential for further clinical application.

To predicate the value of human fetal substantia nigra transplantation in clinical treatment of Parkinson's disease (PD), dissociated cells of substantia nigra from 8-12 week old abortive human fetus were grafted into the neostriatum of 5 adult rhesus monkeys with hemiparkinsonism induced by unilateral injection of MPTP. At 2, 5 and 12 months after transplanting the monkeys were sacrificed for tyrosine hydroxylase (TH) immunocytochemistry to examine the survival and possible synaptic contact of transplanted dopamine (DA) neurons. Transplanted TH immunoreactive cells took a pattern of patches scattered in the neostriatum. Each of the cell patches consisted of 3-10 cells. The TH immunoreactive fiber network was seen in the neostriatum. Electron microscopic survey revealed that TH+ buttons arising from grafted DA neurons formed symmetric or asymmetric synapses with TH- dendritic shafts/spines, and TH+ dendrites were seen to form synapses with TH- axons of the host. Additionally, there were a few synapses formed by TH+ axonal terminals with negative buttons. The results suggest that DA neurons from 8-12 week old abortive human fetus are able to survive grafting into the neostriatum of monkey, a species phylogenetically very close to human, and to establish reciprocal synaptic connectivity with the host even at 2 months post-transplanting. It is, therefore, inferable that embryonic human DA neurons transplanted into human neostriatum may have the same fate as in monkeys.

Unilateral nigrostriatal pathway of rats was destroyed by using injection of 6-hydroxydopamine (6-OHDA), presenting the rotative movement model and transplanting isogenous rat adrenal medullary tissues into their lesioned lateral caudate nucleus. After 2 months, the rotative movement almost abolished by 34% out of the total transplanted rats, and it was significantly reduced by 57% of the same rats. Taking the above rats brain synaptosome, we found the lesioned side, the uptake of tyrosine, dopamine and choline increased significantly, nevertheless, in another group which transplanted with adrenal medullary tissue, the uptake of same neurotransmitters recover to the normal level. In addition, we also found that dopamine (DA2) receptor binding increased remarkably but muscarinic and GABAA receptors binding decreased significantly in lesioned side brain synaptic membrane, while the transplanted group didn't shown such changes.

Five patients of Parkinson were treated by transplanted of adrenal medullary tissue to the corpus striatum of brain. In two cases, the tissue were taken from autologous adrenal medullary and three from homologous adrenal medullary of traumatic dead adults. After this operation most symptoms and signs of the patients appeared to be improved in some degree, but still clearly Parkinsonism. Transplantation of homologous adrenal medullary in the human striatum hasn't been reported. In this series there are no intracranial infection and rejection phenomenon. The therapeutical results of the homograft group were approximately to the autograft. The course and results of this operation were discussed in this paper.