Fetal neocortical transplants in rats: blood-brain barrier development and partial permeability to IgG in long-surviving grafts

Abstract

In previous work, allografts of fetal (E13-16) neocortical tissue transplanted into neocortical lesion cavities in newborn (PND 0-1) rats developed an impermeable blood-brain barrier (BBB) as shown by intravascular administration of horseradish peroxidase and by immunohistochemical staining for endogenous IgG. The present study examines the time course for the formation of the graft BBB by staining for endogenous IgG and also looks at transplants with extended survival times of 1-2 years. At two weeks post-transplantation, the grafts of all ten animals of this group showed evidence of IgG immunoreactivity within the graft parenchyma. This was greatest at the pial surface and adjacent to the ventricular surface of the transplant. By three weeks after transplantation, only four of nine grafts showed graft vessel permeability and this was confined to the area under the pia. At four weeks survival, one of nine grafts showed a small rostral patch of IgG reactivity, and a second animal showed very light, diffuse transplant labeling. The remaining seven animals were devoid of transplant IgG reactivity. At 11.5-28 months, three out of seven grafts had reaction product in the graft, indicating BBB permeability to IgG. In two of these older transplants, permeability was confined to the area around larger blood vessels, while one additional animal (28 months) showed dense labeling immediately below the pial surface. As in normal rats, host brain labeling was only found in circumventricular organs. These results show that circulating macromolecules are excluded from most CNS grafts within the first month of transplantation. This process progresses from the center of grafts and requires the longest time to complete in subpial regions possibly associated with healing of the pia. Some older grafts show leakage of protein which may relate to aging of the transplant or to a low-level graft rejection.