Integrity of the blood-brain barrier in retinal xenografts is correlated with the immunological status of the host

Publisher Website
Google Scholar
Abstract
The purpose of this study was to determine the immunological correlates of blood-brain barrier breakdown in retinal xenografts in rats by utilizing skin grafting to initiate a timed immune response to the transplanted neural tissue. Embryonic day 13–14 CD-1 mouse retinae were grafted into the brainstem parenchyma of neonatal Sprague-Dawley rats. In one group of animals a 100 mm2 CD-1 skin graft was placed on the flank 21 days after the initial neural transplant in order to provoke an immune response to the neural graft. Control animals received no skin graft. Animals were injected with horseradish peroxidase (HRP) in the femoral vein 2–8 days after skin grafting. Brains were processed for Nissl, HRP-tetramethylbenzidine, and anti-M-6, -lymphocyte, -macrophage, and -astrocyte antibodies. Experimental and control animals injected 2–4 days after skin grafting showed no leakage of reaction product in the grafted tissue. A small percentage (one of eight) of 5-day animals showed isolated, patchy leakage, but no evidence of rejection of the neural graft. At 6 days all of the grafts showed evidence of leakage, and 71% of these grafts showed infiltration of lymphocytes. By 7–8 days extensive leakage of HRP and widespread infiltration of lymphocytes and macrophages were clearly evident. The present study demonstrates that blood-brain barrier breakdown is correlated closely with the sequence of immunological rejection of the graft. While these results confirm that a barrier exists in healthy neural transplants, they suggest that immunological factors should be considered in cases in which grafts are not protected by an intact barrier.