Experimental models of demyelination and remyelination

Abstract

Introduction: Experimental animal models constitute a useful tool to deepen our knowledge of central nervous system disorders. In the case of multiple sclerosis, however, there is no such specific model able to provide an overview of the disease; multiple models covering the different pathophysiological features of the disease are therefore necessary.

Development: We reviewed the different in vitro and in vivo experimental models used in multiple sclerosis research. Concerning in vitro models, we analysed cell cultures and slice models. As for in vivo models, we examined such models of autoimmunity and inflammation as experimental allergic encephalitis in different animals and virus-induced demyelinating diseases. Furthermore, we analysed models of demyelination and remyelination, including chemical lesions caused by cuprizone, lysolecithin, and ethidium bromide; zebrafish; and transgenic models.

Conclusions: Experimental models provide a deeper understanding of the different pathogenic mechanisms involved in multiple sclerosis. Choosing one model or another depends on the specific aims of the study.

Keywords: Demyelination; Desmielinización; Encefalitis alérgica experimental; Esclerosis múltiple; Experimental allergic encephalitis; Experimental models; Mielina; Modelos experimentales; Multiple sclerosis; Myelin; Remielinización; Remyelination.

Figure 1

Induced inflammation and demyelination in in vivo models. (A) Induction in autoimmune and/or inflammatory models. An immunostimulator is administered intramuscularly or subcutaneously. Induced inflammation is associated with increased levels of proinflammatory cytokines, T cells, and activated microglia, leading to the formation of reactive oxygen species (ROS), oligodendrocyte and myelin damage, and reactive gliosis and vessel wall alterations, resulting in oedema. This stage is followed by regeneration, where the number of activated cells (astrocytes and microglia) decreases and oligodendrocyte precursor cells migrate mainly from the corpus callosum (CC) or subventricular zone (SVZ) to replace damaged cells and promote remyelination. (B) Induction in demyelination models. Demyelination is induced with chemicals or toxic agents, which are administered orally (diet), locally (intracerebral), intramuscularly, or subcutaneously. After entering the bloodstream, the chemical or toxic agent enters into contact with axons, causing myelin degeneration; this microenvironment induces microglial activation, ROS formation, inflammatory cytokine release, and reactive gliosis. This ultimately leads to the loss of myelin sheaths and myelin-producing cells (oligodendrocytes). This stage is followed by regeneration, where the number of activated cells (astrocytes and microglia) decreases and oligodendrocyte precursor cells migrate mainly from the CC or SVZ to replace damaged cells and promote remyelination.