WHY DO NEURAL TRANSPLANTS SURVIVE - AN EXAMINATION OF SOME METABOLIC AND PATHOPHYSIOLOGICAL CONSIDERATIONS IN NEURAL TRANSPLANTATION

Neural transplantation continues to be a growing field that has advanc ed beyond animal experimentation and into the clinic where trials in p atients with Parkinson's disease are moving forward (14, 30). The rema rkable continuity of the brain grafting paradigm owes to the fact that experimentation and data collection may lend themselves to many disci plines and up-to-date technical analyses. Such procedures can represen t significant advances in our knowledge of brain development and disor ders but extensive investigation remains to be done to ascertain more precisely the cellular and molecular mechanisms by which neural grafts function. There are still many issues in transplantation that need to be resolved, not the least of which is cell survival and enhancement of graft functional capacity. There have been reports that only about 5-10% of dopaminergic neurons in mesencephalic grafts survive (22) and while the numbers of surviving neurons in cortical grafts is not know n, recent studies have indicated that surviving neurons may have abnor mal cellular aspects such as immature dendrites (32), inhibited axonal outgrowth (47), or reduced glycolytic activity (43). In the following commentary, possible cellular mechanisms of graft survival will be ex plored. It will be suggested that based on what is known about both ce rebrovascular pathology and normal brain metabolic development, couple d with the mechanisms of graft vascularization, it is unlikely that ne ural grafts should survive or, at best, survive exhibiting only a modi cum of activity. It will be further suggested that the answer ''...bec ause it is fetal brain...'' to the question-why (or how) do neural gra fts survive?-is an inadequate and presently unexplained one. The survi val and growth of neural grafts is quite complex and may represent, at least in some aspects, unique forms of development, metabolism, and p athology, all of which may differ markedly from the normal in situ sit uation. (C) 1995 Academic Press, Inc.