DEVELOPMENT OF FETAL HIPPOCAMPAL GRAFTS IN INTACT AND LESIONED HIPPOCAMPUS

Functional recovery observed in Parkinson's disease patients following grafting of fetal substantia nigra has encouraged the development of similar grafting therapy for other neurological disorders. Fetal hippo campal grafting paradigms are of considerable significance because of their potential to treat neurological disorders affecting primarily hi ppocampus, including temporal lobe epilepsy, cerebral ischemia, stroke , and head injury. Since many recent studies of hippocampal transplant s were carried out with an aim of laying the foundation for future cli nical applications, an overview of the development of fetal hippocampa l transplants, and their capability for inducing functional recovery u nder different host conditions is timely. In this review, We will summ arize recent developments in hippocampal transplants, especially the a natomical and/or functional integration of grafts within the host brai n under specific host conditions, including a comparison of intact hip pocampus with various types of hippocampal lesions or injury. Improvem ents in grafting techniques, methods for analysis of graft integration and graft function will be summarized, in addition to critical factor s which enhance the survival and integration of grafted cells and alte rnative sources of donor cells currently being tested or considered fo r hippocampal transplantation. Viewed collectively, hippocampal grafti ng studies show that fetal hippocampal tissue/cells survive grafting, establish both afferent and efferent connections with the host brain, and are also capable of ameliorating certain learning and memory defic its in some models. However, the efficacy of intracerebral fetal hippo campal grafts varies considerably in different animal models, dependin g on several factors: the mode of donor tissue preparation, the method of grafting, the slate of host hippocampus at the time of grafting, a nd the placement of grafts within the hippocampus. Functional improvem ent in many models appeared to be caused partially by re-establishment of damaged circuitry and partially by a trophic action of grafts. How ever, exact mechanisms of graft-mediated behavioral recovery remain to be clarified due to the lack of correlative analysis in the same anim al between the degree of graft integration and behavioral recovery. Is sues of mechanisms of action, degree of restoration of host circuitry and amelioration of host pathological conditions will need to be sorte d out clearly prior to clinical use of fetal hippocampal transplants f or susceptible neurological conditions. Copyright (C) 1996 Elsevier Sc ience Ltd.