Comparison of a Chemically Mediated and an Immunologically Mediated Demyelinating Lesion Model

The production of two animal models for the central nervous system degenerative condition multiple sclerosis is described in detail. The first is a chemically mediated noninflammatory demyelinating lesion of the brain stem induced by the injection of a trypanocidal DNA binding dye, ethidium bromide, into the cerebellomedullary cistern. The injection does not involve any physical damage to the blood-brain barrier or the CSF-brain barrier and is simple to perform. The second lesion model is an immunologically mediated demyelinating condition involving the injection of a T-cell line specific for myelin basic protein, followed by injection of a monoclonal antibody against the myelin surface protein, myelin/oligodendrocyte glycoprotein. We describe the production of the antigen-specific T-cell line in detail. This model is characterized by widespread inflammatory infiltrates accompanied by areas of demyelination. Both of these models are produced in the Lewis rat, allowing the direct comparison of mechanisms involved in demyelination and repair in the presence or absence of invading inflammatory cells. Despite the very different etiologies of the two lesion models, they are both acute and result in efficient remyelination.