Multiple sclerosis is an inflammatory demyelinating disorder of the CNS.
Recent studies have suggested diverse mechanisms as underlying
demyelination, including a subset of lesions induced by an interaction
between metabolic insult to oligodendrocytes and inflammatory mediators.
For mice of susceptible strains, cuprizone feeding results in
oligodendrocyte cell loss and demyelination of the corpus callosum.
Remyelination ensues and has been extensively studied. Cuprizone-induced
demyelination remains incompletely characterized. We found that mice
lacking the type 2 CXC chemokine receptor (CXCR2) were relatively
resistant to cuprizone-induced demyelination and that circulating
CXCR2-positive neutrophils were important for cuprizone-induced
demyelination. Our findings support a two-hit process of
cuprizone-induced demyelination, supporting the idea that multiple
sclerosis pathogenesis features extensive oligodendrocyte cell loss.
These data suggest that cuprizone-induced demyelination is useful for
modeling certain aspects of multiple sclerosis pathogenesis.