The Cuprizone Model: Dos and Do Nots

Abstract

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system. Various pre-clinical models with different specific features of the disease are available to study MS pathogenesis and to develop new therapeutic options. During the last decade, the model of toxic demyelination induced by cuprizone has become more and more popular, and it has contributed substantially to our understanding of distinct yet important aspects of the MS pathology. Here, we aim to provide a practical guide on how to use the cuprizone model and which pitfalls should be avoided.

The osmotic demyelination syndrome: the resilience of thalamic neurons is verified with transmission electron microscopy

“…multiple sclerosis or other CNS vascular trauma associated pathologies) making the injurious region damaged free from other immune reactivity 112,113,133,273 and other eventual potent follow-up necrotic neural sequels. 274,275 In ODS, clinical controlled rebalancing sodic osmolality allowed rapid neuron reactivation of their functions that involved, among others, aquaporins.- [276][277][278][279] Experiments that included molecular markers and ultrastructural verifications obviously can further verify and achieve clarifications of the cellular components involved in the regenerative plasticity of this type of mammal and human CNS damage where some data have only been scarce before the advent of recent molecular tools. 103,280 Here, the report demonstrates that the fine structure morphology of the nucleus alone and nucleolus content, as referred abundantly above, as in, 281 can assist to diagnose and understand whether neuron repairs occur in the animal models of neuropathology tested to eventually be translated into potential clinical outcome for some patients who developed defects post ODS.…”

Cuprizone‐induced demyelination triggers a CD8‐pronounced T cell recruitment

“…On the histopathological level, the cuprizone model shares certain similarities with progressive MS pathology (Sen, Mahns, Coorssen, & Shortland, 2019; Zhan et al, 2020) including diffuse white matter injury (Goldberg, Clarner, Beyer, & Kipp, 2015; Kutzelnigg et al, 2005), minor BBB damage (Kirk, Plumb, Mirakhur, & McQuaid, 2003; Merkler et al, 2005), widespread cortical and subcortical demyelination (Goldberg et al, 2015; Peterson et al, 2001) and the absence of focal, perivascular lesions (Lassmann, van Horssen, & Mahad, 2012). Of note, densities of T cells, B cells, and plasma cells positively correlate with the extent of axonal damage and neurodegeneration in progressive MS (Frischer et al, 2009).…”

Advances in 3D neuronal microphysiological systems: towards a functional nervous system on a chip

“…This approach may lend itself for use in studying demyelination and remyelination. Cuprizone and lysophosphatidylcholine (LPC) treatment (Vereyken et al 2009) is commonly used to induce demyelination in the CNS in animal models (Zhan et al 2020). With this drop in myelination, this system can also be used for remyelination assays, which would be especially important for studying relapse-remitting multiple sclerosis.…”