Sequential Intracerebral Transplantation of Allogeneic and Syngeneic Fetal Dopamine-Rich Neuronal Tissue in Adult Rats: Will the First Graft be Rejected?

Abstract

The immune response against intracerebral grafts of allogeneic fetal dopamine-rich tissue was assessed in adult rats. Sprague-Dawley rats, now outbred, but originating from an inbred stock, were given unilateral 6-hydroxy-dopamine lesions of the mesostriatal pathway, and grafted intrastriatally with mechanically dissociated ventral mesencephalic tissue (embryonic day 13-15) obtained from an inbred Lewis strain. Graft survival was assessed by functional recovery of amphetamine-induced rotational behavior on four different occasions postsurgery, and histologically using catecholamine histofluorescence and tyrosine hydroxylase immunohistochemistry. The following groups were analysed: long-term survival of a single allogeneic graft; survival of a first allogeneic graft with a syngeneic second graft; survival of a first allograft combined with a second allogeneic graft; the survival of bilateral allogeneic grafts following a subsequent orthotopic allogeneic skin graft. Evidence for recipient immunization was obtained using an indirect fluorescent antibody detection technique, Simonsen's Spleen Index (S I) test. Viable grafts, giving rise to behavioral compensation, were present after 40 wk in rats from all groups. The “first” allograft always displayed good survival and function, even following a second intracerebral allograft. However, five of nine “second” allogeneic intracerebral grafts survived poorly. In contrast, all secondary syngeneic grafts survived well. Following the application of a subsequent orthotopic allogeneic skin graft in a subgroup of rats, there was a significantly lower survival of grafted dopamine neurons in the “first” graft.