Why do neural transplants survive? An examination of some metabolic and pathophysiological considerations in neural transplantation

Abstract

Neural transplantation continues to be a growing field that has advanced beyond animal experimentation and into the clinic where trials in patients with Parkinson's disease are moving forward (14, 30). The remarkable continuity of the brain grafting paradigm owes to the fact that experimentation and data collection may lend themselves to many disciplines and up-to-date technical analyses. Such procedures can represent significant advances in our knowledge of brain development and disorders 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 known, recent studies have indicated that surviving neurons may have abnormal 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 explored. It will be suggested that based on what is known about both cerebrovascular pathology and normal brain metabolic development, coupled with the mechanisms of graft vascularization, it is unlikely that neural grafts should survive or, at best, survive exhibiting only a modicum of activity. It will be further suggested that the answer "...because it is fetal brain ..." to the question--why (or how) do neural grafts survive?--is an inadequate and presently unexplained one.(ABSTRACT TRUNCATED AT 250 WORDS)