%0 Journal Article
%T IFN-gamma signaling in the central nervous system controls the course of experimental autoimmune encephalomyelitis independently of the localization and composition of inflammatory foci
%A Eunyoung Lee
%A Sarah Chanamara
%A David Pleasure
%A Athena M Soulika
%J Journal of Neuroinflammation
%D 2012
%I BioMed Central
%R 10.1186/1742-2094-9-7
%X We induced EAE in IFN¦Ã-/- mice and bone marrow chimeric mice in which IFN¦ÃR is not expressed in the CNS but is intact in the periphery (IFN¦ÃRCNSKO) and vice versa (IFN¦ÃRperiKO). Blood-brain barrier permeability was determined by Evans blue intravenous administration at disease onset. Populations of immune cell subsets in the periphery and the CNS were quantified by flow cytometry. CNS tissues isolated at various time points after EAE induction, were analyzed by immunohistochemistry for composition of inflammatory foci and patterns of axonal degeneration.Incidence and severity of atypical EAE were more pronounced in IFN¦ÃRCNSKO as compared to IFN¦ÃRperiKO mice. Contrary to what we anticipated, cerebella/brainstems of IFN¦ÃRCNSKO mice were only minimally infiltrated, while the same areas of IFN¦ÃRperiKO mice were extensively populated by peripheral immune cells. Furthermore, the CNS of IFN¦ÃRperiKO mice was characterized by persistent neutrophil-rich foci as compared to IFN¦ÃRCNSKO. Immunohistochemical analysis of the CNS of IFN¦Ã-/- and IFN¦ÃR chimeric mice revealed that IFN¦Ã protective actions are exerted through microglial STAT1.Alterations in distribution and composition of CNS inflammatory foci are not sufficient for the onset of atypical EAE. IFN¦Ã dictates the course of neuroinflammatory disorders mainly through actions exerted within the CNS. This study provides strong evidence that link microglial STAT1 inactivation to vestibular dysfunction.Experimental autoimmune encephalomyelitis (EAE) is the most commonly used animal model for multiple sclerosis (MS). Similar to MS, animals with EAE exhibit activation of immune cells in peripheral immune organs, migration of these cells into the CNS, and establishment of multifocal inflammation, demyelination and damage to neurons and axons. Cumulative axonal loss eventually leads to severe and permanent neurological deficits [1,2]. In classical EAE, most neurological deficits are attributable to spinal cord lesions. Interestingly
%K microglia
%K cerebellum
%K brainstem
%K EAE
%K IFN¦Ã
%K STAT1
%K inflammation
%U http://www.jneuroinflammation.com/content/9/1/7