Fetal Dopaminergic Neurons Transplanted to the Normal Striatum of Neonatal or Adult Rats and to the Denervated Striatum of Adult Rats

Abstract

Fetal ventral mesencephalon from the 15th gestational day was grafted into the striatum of neonatal and adult rats. In one group of adult rats, fetal nigra was transplanted into normal striatum. In a second group, the tissue was transplanted at sites where dopaminergic fibers were denervated with 6-hydroxydopamine. The behavior of the dopaminergic neurons and glial reactions were studied by staining with cresyl violet to localize the transplants and by immunolabeling tyrosine hydroxylase (TH) and glial fibrillary acidic protein. In normal adults, the transplants were small. At the edge of the transplants, TH-positive neurons were packed into clusters, and an interface without any significant crossover of TH-positive fibers was present. Glial reaction was minimal in and around the transplant. In the denervated striatum, transplants were generally larger than those in normal striatum and surrounded by a glial scar. TH-positive neurons were both closely packed and loosely arranged at the periphery of the transplants. Processes could be clearly defined and could be traced to the adjacent host striatum through the TH-free denervated area. In neonates, the transplants were large and at times extended beyond the striatum. Most TH-positive neurons were arranged linearly along the periphery of the transplant. Cell bodies were widely separated and a well-developed neuropil was present. Fibers from the transplant mingled freely with the host striatum without any interface. In all three transplant groups, tracing the TH-positive neurites was easy because they were thicker and coarser than other elements. No apparent glial reaction occurred in the neonates. Thus, the growth and maturation of dopaminergic neurons seemed to vary in different environments. The most conducive environment appears to be neonatal brain in which growth factors are readily available.

Long-term cultured human umbilical cord neural-like cells transplanted into the striatum of NOD SCID mice

“…Some hope is provided by the transplantation studies of Sun et al [38], who demonstrated enhanced survival of neural stem cells into the 6-OHDA lesioned striatum of rats and observed greater survival and more differentiation into TH-positive cells in these mice than in controls. Further evidence that the adult intact striatum is less conducive for transplantation compared to denervated striatum was demonstrated by Sable et al [37], whereas Joannides et al [23] and, as mentioned above, Sun et al [38] demonstrated that pathological conditions enhance neural formation. This may explain why the HUCB cells did not survive to 1 month in our study.…”