BRAIN TRANSPLANTS IN GENETIC ANALYSIS

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Experimental allergic encephalomyelitis (EAE) is an autoimmune, organ specific disorder produced by inoculation of susceptible animals with central nervous system (CNS) antigens in adjuvants. EAE is characterized pathologically by inflammation and demyelination. Susceptibility is genetically determined. Previous studies indicate genetic restriction is not limited to the immune system and suggest restrictive elements at the level of the antigen source and the CNS. The proposed studies are designed to identify the role played by the antigen source, the host immune system and the target CNS in the development of disease. This will be achieved through the use of reciprocal heterotopic brain transplants between EAE susceptible and resistant mice. Transplants of fetal brain tissue will be placed into the anterior chamber of the eye and allowed to mature before disease induction. Animals will be monitored for clinical signs of EAE and histopathologic development of inflammation and demyelination in the native CNS and the transplanted tissues. The integrity of the blood-brain barrier (BBB), a potential site of CNS restriction, will also be evaluated in the native CNS and transplanted tissues by assessing permeability of their vessels to trypan blue dye and horseradish peroxidase when uninoculated and following the induction of disease. These studies, through the employment of transplant technology, will allow phenotypic characterization of the site(s) of genetic restriction in a way not previously possible; separating the role of host immune competence in the development of disease from that of the antigen source and the target CNS. Such information not only provides insight into the pathogenesis of this disease, but also indicates potential sites for therapeutic intervention in the prevention or treatment of such disease.