Patterns of angiogenesis in neural transplant models: II. Fetal neocortical transplants.
Vascular integration between transplanted fetal CNS tissues and host brain is essential for long-term transplant survival. This study compares the time course and mechanism of vascularization in allografts of fetal cerebral cortex inserted either into the fourth ventricle or directly into the parietal cortex or hippocampus of perinatal rats. Recipient animals were administered 3H-thymidine after various postoperative time periods. The tissues were processed for light microscopic autoradiography to determine the temporal pattern of endothelial proliferation at the graft sites. Correlative electron microscopy depicted the morphological changes in transplant vasculature. Some recipients were prelabelled with 3H-thymidine prior to transplantation to determine if host vessels invaded the grafts; conversely, some donor tissues were prelabelled in utero to ascertain if the intrinsic vascular anlagen survived. Intraventricular transplants contained patent vessels, probably originating from the host pia mater, as early as 24 hours postoperative. Intraparenchymal transplants had patent vessels by 72 hours and a more complete network by 5 days. Prelabelling experiments and ultrastructural observations demonstrated that adjacent host pial vessels became incorporated into the perimeter of the intraventricular transplants and later grew centrally into the grafts. Intraparenchymal transplants also contained host vessels that exhibited a similar growth pattern. Intrinsic graft vessels remained viable and continued their development, and presumably anastomosed with the ingrowing host vasculature. Temporal labelling studies revealed that both vessel populations attained their highest proliferative rates within 72 hours after transplantation. This study demonstrates that the vasculature which develops within both intraventricular and intraparenchymal fetal CNS transplants is chimeric, consisting of intrinsic fetal vasculature and proliferating host vessels. The mechanism of transplant vascularization may be significant with regard to astrocytic, immunological, or blood-brain-barrier characteristics at these transplantation sites.