Intracephalic embryonic neural implants in the adult rat brain. I. Growth and mature organization of birainstem, cerebellar, and hippocampal implants

Abstract

Abstract Implants of embryonic CNS tissue, dissected from the developing brainstem, cerebellum, and hippocampus of rat fetuses, were analyzed after 2–14 months survival in an intracephalic transplantation cavity in adult host rats. The mature anatomical organization of the implants was studied in specimens taken from early (embryonic day, (E) 12–14) and late (E17–20) gestational stages and compared with the results previously obtained in explant cultures and in experiments with transplants to the anterior eye chamber and to the brains of neonatal rats. The resulting volume of the implanted tissue is dependent on the gestational age of the donor fetus. For all regions analyzed the early gestational tissue develops to become larger than the late gestational tissue. Moreover, tissue dissected from different regions of the neuraxis at a specific developmental time point exhibits differing amounts of proliferation within the intracephalic cavity of the host. Though all early gestation transplants demonstrate continued cell genesis as indicated by their subsequent increase in size, late gestation brainstem specimens fail to show an increase in tissue volume and the late gestation cerebellar implants actually exhibit a reduction in final size. Early gestation hippocampal transplants demonstrate the greatest increase in tissue volume (over 3,800%) and completely fill the intracephalic cavity with no apparent encroachment upon the host CNS tissue. However, hydrocephalus was present in one host animal which contained a transplant contaminated by connective tissue that obstructed the lateral ventricle. Each implanted CNS region demonstrates cytoarchitectural features characteristic for the specific region in vivo. The results demonstrate that (1) neuroepithelial cells in the implants taken from various regions of the neuraxis can continue cell genesis after transplantation to an adult CNS environment; cells are capable of normal migration within the implant; and they continue to differentiate to produce neurons with many of their normal in vivo morphologic characteristics; (2) neurons generated before the embryonic tissue is taken for transplantation can, at least to some degree, survive and retain their cytoarchitectural features in the new environment; (3) many characteristics of the intrinsic organization and three‐dimensional architecture of each CNS region can develop even in an ectopic intracephalic site in the adult host. These observations indicate that the in cerebro implantation technique can provide an extremely valuable experimental preparation in which to analyze various aspects of development which may influence the organization of specific CNS regions, including parameters that regulate the morphology of individual neurons. The developmental questions that can be explored with this technique should complement those which can be addressed with in vitro explant or reaggregation procedures and with the intraocular grafting technique. In particular, the intracephalic implantation technique should prove valuable for obtaining new insights into cellular events that determine the complex three‐dimensional organization of the mammalian CNS during development.