Dr. Hoffer and his colleagues will conduct a multidisciplinary series of behavioral, electrophysiological, electrochemical and cytochemical studies on the development of fetal neural cells grafted to the brain. In a series of experiments involving rat fetal catecholamine-containing allografts transplanted to basal ganglia - (1) innervation state and appropriateness of the host target, (2) immune status of the host, (3) availability of peptide co-transmitters, (4) action of trophic substances such as bFGF, (5) interaction with chronically administered dopamine agonists, and (6) activity of grafted dopamine terminals in unanesthetized animals - will be examined. In a series of experiments involving human fetal catecholamine-containing xenografts transplanted to basal ganglia of immunoincompetent rats, many of the same parameters listed above will be studied. In addition, experiments will be carried out to determine (1) the feasibility of cryopreservation or """"""""hibernation of donor tissue and (2) mechanisms of MPTP neurotoxicity on such xenografts. In addition, collaborative studies will be carried out on genetically modified cells altered to synthesize and secrete trophic factors such as nerve growth factor and fibroblast growth factor. Such cells will be grafted to rat basal ganglia sites either alone or with fetal neural cell co-grafts.
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