THE DISTRIBUTION OF INFLAMMATORY DEMYELINATED LESIONS IN THE CENTRAL-NERVOUS-SYSTEM OF RATS WITH ANTIBODY-AUGMENTED DEMYELINATING EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS

Experimental allergic encephalomyelitis (EAE) has long been studied as an animal model of the human demyelinating disease Multiple Sclerosis . However, EAE induced in the Lewis rat by injection of myelin basic p rotein (MBP), or MBP-specific T-lymphocytes, is primarily an inflammat ory condition of the central nervous system (CNS) with little or no de myelination. In EAE models in which demyelination does result, it is e ither not very widespread or is unpredictable in its degree and locati on. In this study we have produced antibody-augmented demyelinating EA E (ADEAE) in the Lewis rat by injection of activated MBP-specific T-ly mphoblasts, followed by injection 4 days later of a monoclonal antibod y against myelin/oligodendrocyte glycoprotein, an extrinsic protein of myelin. We have documented the extent and location of inflammatory ce ll infiltrates and demyelination throughout the CNS using histochemist ry, immunofluorescence, and image analysis. Perivascular inflammatory infiltrates were seen in the deep cerebellar white matter and in the f olia. Perivascular, periventricular, and subpial inflammation was wide spread throughout the pons/medulla and at all levels of the spinal cor d. Very little inflammation was apparent in the forebrain. MBP immunof luorescence demonstrated extensive areas of periventricu lar demyelina tion in the forebrain around the third ventricle. Both periventricular and perivascular lesions were commonly observed in the cerebellum and pons/medulla. The extent of demyelination in the spinal cord increase d caudally with large confluent areas of subpial demyelination seen th roughout the lumbar cord. The extensive and reproducible distribution of inflammatory demyelinating lesions in ADEAE provide the possibility to select areas of the CNS for more detailed analysis of the cellular changes that accompany demyelination and remyelination. (C) 1994 Acad emic Press, Inc.