Intracerebral transplantation: basic and clinical applications to the neostriatum

Many studies have used the intracerebral transplantation technique to study the neostriatum. Most of this work has been conducted in two well-characterized animal models of striatal dysfunction: the rat model of Huntington's disease (striatal damage) and the rat model of Parkinson's disease (damage of dopaminergic nigrostriatal afferents). In animals with striatal damage, fetal striatal tissue implanted into the neostriatum (homotypic transplants) displays a remarkable anatomical and functional incorporation into the host brain. These homotypic grafts also induce a wide range of behavioral improvements in experimental animals. In contrast, fetal substantia nigra neurons implanted into the dopamine-depleted neostriatum (heterotypic transplants) generally show a more restricted integration into the host brain and elicit fewer behavioral improvements. Nonetheless, the ability of grafted fetal neurons to survive, differentiate, and partially reconstruct an appropriate and functional neurocircuitry with host systems indicates that there are factors within the adult brain that promote neuronal development and regeneration. Such results have encouraged the clinical use of intracerebral grafts for the treatment of Parkinson's disease. Recent studies have emphasized the use of genetically modified cells and neural cell lines as alternative populations to study and repair the central nervous system.