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.