PERMEABILITY OF THE BLOOD-BRAIN-BARRIER TO PROTEIN AND [H-3] GABA IN INTRAPARENCHYMAL FETAL CNS TISSUE GRAFTS

In the present study solid grafts of rat fetal neocortex or substantia nigra were transplanted into young adult rat cortex or striatum, To s tudy the permeability to protein and potential changes in the blood-br ain barrier (BBB), HRP was administered intravascularly or, to examine endogenous protein exudation, noninjected animals were evaluated afte r immunocytochemical stain for rat serum albumin. In addition, [H-3]GA BA, a neurotransmitter that does not cross the BBB, was systemically a dministered to cortical graft-bearing hosts in order to determine if a barrier to small potentially bioactive compounds was present. Postope rative periods ranged between 1 week and 15 months for the cortical gr afts and between 1 week and 8 months for nigral grafts; the experiment s were repeated several times at the same time point in order to deter mine the potential for variability in the model systems. The results s how that a high percentage (80%) of both neocortical and nigral grafts lack a complete BBB to protein up to 2-3 weeks postoperative. After t his time the majority of neocortical grafts were impermeable to protei n yet 20-30% of longer-term specimens showed variable degrees of perme ability to protein; permeability to [H-3]GABA, which manifested in the transmitter being sequestered by graft neurons, was observed only up to 4 weeks postoperative, Nigral grafts after 4 weeks postoperative sh owed negligible permeability to serum protein. Although in all early C NS grafts protein permeation is extensive in both graft and adjacent h ost, the mature host brain resolved the exudation far more efficiently so that the reaction appeared exclusively in the graft or interface a nd not in the host by 2-3 weeks, suggesting that the graft tissue may lack appropriate mechanisms for clearance of extracellular materials, It is unclear why this phenomenon occurred consistently but in a minor ity percentage of cortical specimens. It is suggested that either fran k pathology or immunopathology provides a subtle and incomplete reject ion process that allows the interface vessel to be permeable over the life of the graft. Since nigral grafts appeared to have significantly less BBB dysfunction variation it is possible that the maturation leve ls or the ontogeny between different graft sources may play a role in differing responses to injury or vascular problems after transplant su rgery. (C) 1996 Academic Press, Inc.