Long-term survival of mesencephalic and striatal cells from mouse embryos in dissociated primary cultures is described. Catecholaminergic neurons in mesencephalic culutres were identified histochemically and by measuring [3H]dopamine uptake and synthesis from [3H]tyrosine. According to experiments using specific inhibitors of catecholamine uptake, at least two-thirds of the catecholaminergic neurons are dopaminergic. These neurons differentiated whether or not striatal target cells were present, but striatal cells stimulated the development of the dopaminergic neurons. [3H]Dopamine uptake was increased by at least 2-fold regardless of the age of the cocultures (4-15 days). Enhanced [3H]dopamine synthesis was also observed (at least 2-fold) at later times (12-15 days).

✓ Parkinsonism or hemiparkinsonism was induced by administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in four rhesus monkeys, which then received homologous fetal mesencephalon implants into the caudate nuclei. Cavities were prepared in the medial caudate nucleus 2 to 5 weeks before the fetal grafts were implanted. Control studies were conducted in unoperated MPTP-treated animals. Significant behavioral improvement, which occurred within weeks of implantation of fetal mesencephalon, was sustained for up to 7 months. No recovery was seen in the unoperated control animals. Histological examination revealed numerous surviving tyrosine hydroxylase (TH)-immunoreactive cell bodies. In addition to the graft, abundant TH-immunoreactive fibers were observed in the host caudate nucleus ventral to the region of the implanted and the nonimplanted cavities. Since TH-immunoreactive cell bodies of the substantia nigra compacta (A-9 cells) were destroyed by MPTP treatment and the ventral tegmental area (A-10) remained intact, it is concluded that sprouting of remaining host dopaminergic fibers occurs. These newly formed fibers appeared to emanate from the mesolimbic projection to the striatum. It is likely that the newly sprouted dopaminergic fibers account for the motor improvement elicited by precavitation and fetal mesencephalon implantation. These results suggest that the mechanism of recovery of parkinsonian primates after implantation of fetal dopaminergic tissue into the caudate nucleus is by stimulation of sprouting from host neurons. They also suggest that, with identification of the factors responsible for the formation of the new dopaminergic neuronal processes and with further development, tissue implantation may be an effective therapy for Parkinson's disease in humans.

Research on stem cells has developed as one of the most promising areas of neurobiology. In the beginning of the 1990s, neurogenesis in the adult brain was indisputably accepted, eliciting great research efforts. Neural stem cells in the adult mammalian brain are located in the ‘neurogenic’ areas of the subventricular and subgranular zones. Nevertheless, many reports indicate that they subsist in other regions of the adult brain. Adult neural stem cells have arisen considerable interest as these studies can be useful to develop new methods to replace damaged neurons and treat severe neurological diseases such as neurodegeneration, stroke or spinal cord lesions. In particular, a promising field is aimed at stimulating or trigger a self‐repair system in the diseased brain driven by its own stem cell population. Here, we will revise the latest findings on the characterization of active and quiescent adult neural stem cells in the main regions of neurogenesis and the factors necessary to maintain their active and resting states, stimulate migration and homing in diseased areas, hoping to outline the emerging knowledge for the promotion of regeneration in the brain based on endogenous stem cells.