Neurotransmitters and cytokines in CNS pathology

This chapter demonstrates an in vitro model for oligodendrocyte cell death that may be relevant to events in formation of lesions in multiple sclerosis (MS). It involves cell contact to oligodendrocytes with activated, viable microglia, surface tumor necrosis factor (TNF)-α, surface adhesion molecules, and production of NO. MS is a demyelinating disease of the central nervous system, in which myelin sheaths and the myelin-producing cells, oligodendrocytes, are destroyed. There is an accumulation of activated microglia and inflammatory macrophages as well as presence of proinflammatory cytokines such as TNF-α and interferon gamma (IFN-γ) at the lesion edge. The asymmetry of the pathology of these lesions with myelin loss and oligodendrocyte death in the wake or trailing edge of the growing lesion, but not at the leading edge of the lesion, suggests that the plaque formation is cell-mediated. Indeed, proliferation of oligodendrocytes is seen just beyond the plaque margin. Precise mechanisms of TNF-α and intercellular adhesion molecule-l/ leukocyte functional antigen-l participation and the nature of the susceptibility of the oligodendrocyte are presently being studied. © 1994, Academic Press Inc. All rights reserved.