THE EFFECTS OF DONOR STAGE ON THE SURVIVAL AND FUNCTION OF EMBRYONIC STRIATAL GRAFTS IN THE ADULT-RAT BRAIN .1. MORPHOLOGICAL-CHARACTERISTICS

The effects of the stage of donor embryos on the survival of grafts fr om different neuronal cell types have been well documented. Indeed, th is parameter has been shown to be highly important in the survival and function of transplants of various tissues of the CNS. However this q uestion has not been addressed in grafts of embryonic striatal tissue transplanted into animal models of Huntington's disease. In this study , rats which had received a unilateral ibotenic acid lesion in the dor sal striatum received grafts from a standard dissection of embryonic s triatal primordium taken from donors of embryonic stage either E14, E1 6, E17 or E19 days. Three months after transplantation six rats from e ach group were killed for analysis of graft survival and morphology. T he remaining animals in each group were killed between 10 and 14 month s after grafting. Graft morphology was detected using a range of marke rs including: acetylcholinesterase and Cresyl Violet, the 32,000 mol. wt dopamine- and cyclic AMP-regulated phosphoprotein (DARPP-32), tyros ine hydroxylase and striatally-enriched phosphatase. All the grafts fr om different donor stages survived well at both time-points and Cresyl Violet staining indicated neuronal cell types spread throughout the g rafts. The transplants were seen to have a characteristic ''patchy'' a ppearance with areas of dense AChE activity and DARPP-32 immunopositiv ity interspersed with areas of much lighter expression. These areas al so co-localized consistently with striatally-enriched phosphatase and tyrosine hydroxylase expression, indicating that they comprised the st riatal-like compartment of the graft (the so called P zones, containin g cells of the mature striatum), and receiving specific afferent input from the host dopaminergic system. There was no significant differenc e in total graft volume, when comparing individual groups at both time -points from grafting. However, when comparing the volume of the P zon es, the striatal primordium from the youngest donor stages (E14 and E1 6) produced grafts with a significantly higher proportion of striatal- like tissue. Therefore, in order to increase the proportion of striata l tissue within these grafts, tissue from younger embryonic donors sho uld be used. This has important implications in the application of thi s model towards clinical trials in Huntington's disease. (C) 1997 IBRO . Published by Elsevier Science Ltd.