DEVELOPMENT OF AN INTACT BLOOD-BRAIN-BARRIER IN BRAIN-TISSUE TRANSPLANTS IS DEPENDENT ON THE SITE OF TRANSPLANTATION

Transplantation of fetal septal forebrain tissue was performed to the anterior chamber of the eye, or intracranially to the rostral hippocam pal formation in rats, to evaluate the impact of transplantation site on the development of an intact blood-brain barrier (BBB), The tissue was studied at 1, 2, 3, and 4 wk following transplantation by means of intravenous injection of Trypan blue, which is a vital stain not norm ally penetrating the BBB, as well as with an antibody specifically dir ected against the rat BBB, SMI71, In the intraocular septal transplant s, there was a significant leakage of Trypan blue 1 wk postgrafting, a ssociated with a few laminin-immunoreactive blood vessels that did not contain any SMI71-immunoreactivity However, at 2 wk postgrafting, the intraocular grafts exhibited an extensive plexus of thin-walled blood vessels expressing SMI71 immunoreactivity and no Trypan blue leakage, Thus, it appeared that a BBB had developed to some degree by 2 wk pos tgrafting in oculo, In the intracranial grafts, on the other hand, Try pan blue leakage could be seen as long as 3 wk postgrafting, and a den se plexus of blood vessels with SMI71 immunoreactivity was first seen at 4 wk postgrafting, Thus, the development of Trypan blue impermeabil ity was delayed with 1 to 2 wk in the intracranial versus the intraocu lar grafts, Control experiments using psychological stress in adult ra ts as a means to transiently disrupt the BBB revealed that an increase in Trypan blue leakage correlated well with the disappearance of SMI7 1 immunoreactivity, Taken together, these studies demonstrate that the site of transplantation can influence the development of an intact BB B in neural tissue grafts.