Embryonic mesencephalic and striatal co-grafts: Development of grafted dopamine neurons and functional recovery

Previous neural grafting studies have shown that embryonic dopamine neurons survive transplantation into the parenchyma of the brain; however, fiber outgrowth from those cells is often limited to the immediate vicinity of the graft. More extensive outgrowth is desirable for promoting and maintaining functional recovery of damaged neural systems in animal models as well as human neurodegenerative disorders. The present study examined the possibility of stimulating fiber outgrowth of grafted neurons by simultaneously grafting dopamine neurons with their embryonic target cells. Subsequent functional recovery was evaluated in concert with morphological characteristics of these grafts. Co-grafts of embryonic mesencephalic and striatal cells were implanted into the DA-denervated striatum of rats previously given unilateral 6-hydroxydopamine lesions of the nigrostriatal pathway. Two types of co-grafts were implanted into the DA-denervated striatum: mixed or separate cell suspensions. Tyrosine hydroxylase immunocytochemical analysis of brain sections containing co-grafts revealed extensive arborization of TH-positive neurons in both types of co-grafts. When mesencephalic and striatal nerve cells were implanted into separate sites, TH-positive neurons extended projections that appeared to preferentially reach regions occupied by embryonic striatal neurons. Moreover, the average size of TH-positive cell bodies found in mixed or separate co-grafts was significantly larger than the size of those found in single mesencephalic grafts. Amphetamine-induced rotational behavior was used to assess the degree of functional recovery. In the majority of co-grafted animals, rotational behavior was attenuated by 3 weeks and reversed (amphetamine-induced contralateral rotation) by 5 weeks. Taken together, these behavioral and morphological data indicate that embryonic striatal neurons may provide a trophic environment for the development and function of mesencephalic neurons when co-grafted into the parenchyma of the DA-denervated striatum.