The Distribution of Inflammatory Demyelinated Lesions in the Central Nervous System of Rats with Antibody-Augmented Demyelinating Experimental Allergic Encephalomyelitis

Abstract

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 protein (MBP), or MBP-specific T-lymphocytes, is primarily an inflammatory condition of the central nervous system (CNS) with little or no demyelination. In EAE models in which demyelination does result, it is either not very widespread or is unpredictable in its degree and location. In this study we have produced antibody-augmented demyelinating EAE (ADEAE) in the Lewis rat by injection of activated MBP-specific T-lymphoblasts, followed by injection 4 days later of a monoclonal antibody against myelin/oligodendrocyte glycoprotein, an extrinsic protein of myelin. We have documented the extent and location of inflammatory cell infiltrates and demyelination throughout the CNS using histochemistry, immunofluorescence, and image analysis. Perivascular inflammatory infiltrates were seen in the deep cerebellar white matter and in the folia. Perivascular, periventricular, and subpial inflammation was widespread throughout the pons/medulla and at all levels of the spinal cord. Very little inflammation was apparent in the forebrain. MBP immunofluorescence demonstrated extensive areas of periventricular demyelination 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 increased caudally with large confluent areas of subpial demyelination seen throughout 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.