An Animal Model of Cortical and Callosal Pathology in Multiple Sclerosis

Abstract

The pathological and radiological hallmarks of multiple sclerosis (MS) include multiple demyelinated lesions disseminated throughout the white matter of the central nervous system (CNS). More recently, the cerebral cortex has been shown to be affected in MS, but the elucidation of events causing cortical demyelination has been hampered by the lack of animal models reflecting such human cortical pathology. In this report, we have described the presence of cortical gray matter and callosal white matter demyelinating lesions in the chronic experimental autoimmune encephalomyelitis (EAE) mouse model of MS. Similar to the pathological lesions of MS patients, EAE lesions have been classified as type I-leukocortical, type II-intracortical and type III-subpial. All of these lesions had varying degrees of demyelination, inflammatory cells and reactive astrocytes. Similar to MS, cortical layers during EAE showed demyelination, microglia activation, synaptic protein alterations and apoptotic cells. In addition, the callosal white matter during EAE had many inflammatory demyelinating lesions and axon degeneration. Functional electrophysiological conduction analysis showed deficits in both myelinated and unmyelinated callosal axons during early and late EAE. The chronic EAE mouse model has features that mimic cortical and callosal pathology of MS, and can be potentially used to screen agents to prevent these features of disease.

Multiple functional therapeutic effects of the estrogen receptor β agonist indazole-Cl in a mouse model of multiple sclerosis

“…Similar to previous observations, corpus callosum (CC) of EAE mice showed many periventricular infiltrating lesions around blood vessels and scattered throughout white matter, accompanied by microglia/macrophage and reactive astrocyte accumulation and fewer enhanced green fluorescent protein on the proteolipid promoter (PLP_EGFP + ) OLs (13,14). EAE CC pathology resembles that observed in EAE DC.…”

“…3 I, c and d). Similarly, a decrease in MBP + CC intensity was observed in vehicle-treated mice (13) (Fig. 3 II, A).…”

“…Our previous work reveals reduced axon numbers and myelination in the DC and CC by EAE day 21 (10,13). Ind-Cl effects on axonal pathology and demyelination were evaluated.…”

“…4H). (5,13,18). Increased callosal OLs in Ind-Cl-treated EAE mice could be a result of decreased OL apoptosis and/or increased OL survival.…”

Efeito dos componentes salivares do mosquito <i>Aedes aegypti</i> na biologia de macrófagos e potenciais aplicações terapêuticas.

“…Dessa forma, o modelo de EAE é um modelo bastante útil uma vez que muitas das patologias observadas no SNC de animais com EAE apresentam uma forte similaridade com aquelas encontradas no SNC dos pacientes com EM (HOHLFELD e WEKERLE, 2001;MANGIARDI et al, 2011;MCCARTHY et al, 2012;ROBINSON et al, 2014).…”