SEQUENTIAL INTRASTRIATAL GRAFTING OF ALLOGENEIC EMBRYONIC DOPAMINE-RICH NEURONAL TISSUE IN ADULT-RATS - WILL THE 2ND GRAFT BE REJECTED

An important issue in clinical neural grafting is whether a second ins triatial allograft can survive well in a patient who has received an a llograft before. In this study, the survival, immunogenicity and funct ion of intrastriatal grafts of allogeneic or syngeneic embryonic dopam ine-rich tissue in rats which had previously received either an intras triatal allo- or syn-graft or sham injections were examined. The first graft tissue was taken from inbred Lewis or Sprague-Dawley rat embryo s and grafted into an intact straitum of adult Sprague-Dawley rats sub jected to a unilateral 6-hydroxydopamine lesion on the contra-lateral side. Eight weeks after the first transplantation, either allogeneic o r syngeneic tissue was grafted as dissociated tissue into the dopamine depleted striatum. The function of the second grafts was assessed by rotational asymmetry at two different time points, i.e. eight and 14 w eeks after the second transplantation. There were significant reductio ns of rotational asymmetry in all groups over time, but no significant difference between groups. Tyrosine hydroxylase immunocytochemistry w as used to assess dopamine cell survival and graft size. Statistical a nalysis revealed no significant difference in the mean number of tyros ine hydroxylase immunoreactive cells or the mean volume of the second grafts placed on the right side (lesioned side) between groups. Monocl onal antibodies were used to evaluate cellular immune reactions and th e major histocompatibility complex class I and class II expression in and around grafts. No major histocompatibility complex class I express ion was seen in any of the graft combinations. The expression of the m ajor histocompatibility complex class II antigens was generally higher in patches in and around the second allograft of rats which had previ ously received an allograft than that in and around any other type of grafts. However, the expression of the major histocompatibility comple x class II antigens was low throughout the grafts and did not appear a s marked perivascular infiltrates. All the major histocompatibility co mplex class II positive cells displayed a microglia-like morphology, s upported by the parallel microglia and macrophage-specific OX-42 immun ostaining. The results show that there is no marked on-going immune re actions in or around the implantation site in any group fourteen weeks after a second transplantation. It may be concluded, therefore, that sequential allografting, using stereotaxic implantation of dissociated embryonic neural tissue into the striatal parenchyma, is possible to perform without a major risk of graft rejection, provided that an atra umatic technique is used.