IMPROVED GRAFT-SURVIVAL AND STRIATAL REINNERVATION BY MICROTRANSPLANTATION OF FETAL NIGRAL CELL-SUSPENSIONS IN THE RAT PARKINSON MODEL

A microtransplantation approach has been used in order to achieve more complete reinnervation of the dopamine denervated rat striatum by fet al nigral cell suspensions injected into multiple striatal sites. A to tal of 450,000 cells, obtained from the ventral mesencephalon of embry onic day 14 rat fetuses, were implanted either in the conventional way as two 1.8-mu l deposits centrally in the head of the caudate-putamen ('Macro grafts'), or as eighteen 0.2-mu l deposits disseminated over six needle penetrations in the same area using a 50-70 mu m glass capi llary tip ('Micro grafts'). Non-grafted lesioned rats served as contro ls. Dopamine neuron survival (as assessed by tyrosine hydroxylase immu nohistochemistry at 4 months after transplantation) was 2.8-fold great er in the Micro grafts as compared to the Macro grafts. Striatal dopam ine tissue levels (determined in a separate group of rats) was increas ed 2.5-fold in the head of the caudate-putamen (from 12.5% of normal i n the Macro graft group to 30% of normal in the Micro graft group). Co nsistent with this, the overall graft-derived tyrosine hydroxylase pos itive fiber outgrowth was more extensive in the Micro graft group and covered larger areas of the previously denervated caudate-putamen. The results show that distribution of the fetal nigral tissue in multiple small deposits provides for increased dopamine neuron survival, proba bly because of a closer contact between the implanted cells and the su rrounding host striatal tissue in the small-sized graft deposits. Less bleeding and necrosis at the implantation site may also have contribu ted to this effect. The present microtransplantation procedure is an e fficient means to increase overall dopamine neuron survival and to ach ieve more complete reinnervation of the denervated striatum in the rat Parkinson model. It also substantially increased the reproducibility of DA graft survival between animals.