title: Inflammatory response and chemokine expression in the white matter corpus callosum and gray matter cortex region during cuprizone-induced demyelination.
abstract: Brain inflammation plays a central role in multiple sclerosis (MS). Besides lymphocytes, the astroglia and microglia mainly contribute to the cellular composition of the inflammatory infiltrate in MS lesions. Several studies were able to demonstrate that cortical lesions are characterized by lower levels of inflammatory cells among activated microglia/macrophages. The underlying mechanisms for this difference, however, remain to be clarified. In the current study, we compared the kinetics and extent of microglia and astrocyte activation during early and late cuprizone-induced demyelination in the white matter tract corpus callosum and the telencephalic gray matter. Cellular parameters were related to the expression profiles of the chemokines Ccl2 and Ccl3. We are clearly able to demonstrate that both regions are characterized by early oligodendrocyte stress/apoptosis with concomitant microglia activation and delayed astrocytosis. The extent of microgliosis/astrocytosis appeared to be greater in the subcortical white matter tract corpus callosum compared to the gray matter cortex region. The same holds true for the expression of the key chemokines Ccl2 and Ccl3. The current study defines a model to study early microglia activation and to investigate differences in the neuroinflammatory response of white vs. gray matter.
authors.affiliation: Institute of Neuroanatomy, Faculty of Medicine, RWTH Aachen University, Wendlingweg 2, 52074, Aachen, Germany.
authors.forename: J P
authors.initials: JP
authors.lastname: Buschmann
authors.forename: K
authors.initials: K
authors.lastname: Berger
authors.forename: H
authors.initials: H
authors.lastname: Awad
authors.forename: T
authors.initials: T
authors.lastname: Clarner
authors.forename: C
authors.initials: C
authors.lastname: Beyer
authors.forename: M
authors.initials: M
authors.lastname: Kipp
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000276:immunology* / Q000473:pathology; D018932:Chemokine CCL2 / Q000235:genetics* / Q000276:immunology; D054405:Chemokine CCL3 / Q000235:genetics* / Q000276:immunology; D003337:Corpus Callosum / Q000276:immunology* / Q000473:pathology; D003471:Cuprizone / Q000633:toxicity*; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000276:immunology*; D004195:Disease Models, Animal; D004660:Encephalitis / Q000139:chemically induced / Q000235:genetics / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000276:immunology / Q000473:pathology; D008996:Monoamine Oxidase Inhibitors / Q000633:toxicity; D009103:Multiple Sclerosis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D009836:Oligodendroglia / Q000276:immunology / Q000473:pathology
chemical_list: C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D054405:Chemokine CCL3; D008996:Monoamine Oxidase Inhibitors; D003471:Cuprizone