The
cuprizone model is a widely used model to study the pathogenesis of
multiple sclerosis (MS). Due to the selective loss of mature oligodendrocytes and myelin, it is mainly being used to study
demyelination and the mechanisms of remyelination, as well as the efficiency of compounds or
therapeutics aiming at remyelination. Although early investigations using high dosages of
cuprizone reported the occurrence of
hydrocephalus, it has long been assumed that
cuprizone feeding at lower dosages does not induce changes at the blood-brain barrier (BBB). Here, by analyzing BBB ultrastructure with high-resolution electron microscopy, we report changes at astrocytic endfeet surrounding vessels in the brain parenchyma. Particularly,
edema formation around blood vessels and swollen astrocytic endfeet already occurred after feeding low dosages of
cuprizone. These findings indicate changes in BBB function that will have an impact on the milieu of the central nervous system (CNS) in the
cuprizone model and need to be considered when studying the mechanisms of de- and remyelination.