Alterations of the blood-brain barrier after transplantation of autonomic ganglia into the mammalian central nervous system.

ABSTRACT

Autonomic (superior cervical) ganglia, the vessels of which are freely permeable to macromolecules, from mature rat donors (allografts or autografts) were transplanted to different sites in the central nervous system (CNS). Minimal trauma was caused by grafts into the IVth ventricle while grafts to intraparenchymal locations such as cerebral cortex and spinal cord were necessarily traumatic and produced glial scarring. Postoperative periods were between 4 weeks and 30 months. A potentially significant aspect of neural transplantation is the functional vascular connections between host and graft. It is highly likely that grafting procedures alter the blood-brain barrier (BBB) in the recipient brain. In order to determine permanent BBB changes, the glycoprotein horseradish peroxidase (HRP) (M.W. 40,000) was injected intravascularly for circulation periods ranging between 50 seconds and 90 minutes. Protein exudation was monitored by using the chromogens DAB and the highly sensitive TMB. All autonomic ganglia transplants, regardless of postoperative or HRP circulation times, were permeable to the injected protein; no qualitative differences were found between allografts and autografts. The blood-borne protein traversed the autonomic graft and infiltrated into the host brain for distances between 200 micron in intraparenchymal grafts to over 1 mm in intraventricular grafts; a smaller exudate was found in the intraparenchymal model than in the intraventricular site probably due to glial scarring that impeded the protein movement in the interstitial spaces. Significantly, TMB demonstrated that the systemic protein entered the cerebrospinal fluid. HRP was detected on the ventricular floor and in the perivascular spaces of the microvasculature. Transplantation of an autonomic ganglion into the brain provides a biological portal that bypasses normal barriers to macromolecules. The vascular and extracellular confluences between host and graft could provide direct access for systematically administered substances to enter brain regions where they, normally, would be excluded.