Selective sprouting of injured dopaminergic neurons induced by embryonic brain grafts

Following 6-hydroxydopamine lesions of the catecholaminergic fibers in the medial forebrain bundle (mfb), little fiber regrowth occurs through the lesion site. However, if grafts of embryonal neocortical tissue are placed into the lesion site 2 weeks after the initial lesions, host catecholaminergic fibers sprout through the lesion site into the graft over the ensuing 2 months. The present study examined the origin of these fibers. Both tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (D beta H) immunoreactive fibers grew into grafts placed in the intact mfb. However, when mfb lesions were made prior to grafting, TH-immunoreactive fiber ingrowth was similar to that seen without an mfb lesion. Conversely, there was only limited D beta H immunoreactive fiber ingrowth. Similarly, such grafts contained patches of [3H]mazindol binding to dopamine transporter sites, while binding of [3H]desipramine to norepinephrine transporters was not demonstrable. Thus, embryonic brain grafts promote significant sprouting of injured dopaminergic axons and limited sprouting of injured noradrenergic/adrenergic fibers, neither of which would otherwise occur. This suggests the presence of a trophic interaction or permissive milieu provided by the graft which is relatively selective for dopamine neurons.