English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Plus monthly

Global: Zendy Tools annual

Global: Zendy Tools monthly

Global: Zendy Free Plan

Background  Murine experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis, presents typically as ascending paralysis. However, in mice in which interferon-gamma (IFNγ) signaling is disrupted by genetic deletion, limb paralysis is accompanied by atypical deficits, including head tilt, postural imbalance, and circling, consistent with cerebellar/vestibular dysfunction. This was previously attributed to intense cerebellar and brainstem infiltration by peripheral immune cells and formation of neutrophil-rich foci within the CNS. However, the exact mechanism by which IFNγ signaling prohibits the development of vestibular deficits, and whether the distribution and composition of inflammatory foci within the CNS affects the course of atypical EAE remains elusive.    Methods  We induced EAE in IFNγ-/- mice and bone marrow chimeric mice in which IFNγR is not expressed in the CNS but is intact in the periphery (IFNγR CNS KO) and vice versa (IFNγR peri KO). 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.    Results  Incidence and severity of atypical EAE were more pronounced in IFNγR CNS KO as compared to IFNγR peri KO mice. Contrary to what we anticipated, cerebella/brainstems of IFNγR CNS KO mice were only minimally infiltrated, while the same areas of IFNγR peri KO mice were extensively populated by peripheral immune cells. Furthermore, the CNS of IFNγR peri KO mice was characterized by persistent neutrophil-rich foci as compared to IFNγR CNS KO. Immunohistochemical analysis of the CNS of IFNγ-/- and IFNγR chimeric mice revealed that IFNγ protective actions are exerted through microglial STAT1.    Conclusions  Alterations in distribution and composition of CNS inflammatory foci are not sufficient for the onset of atypical EAE. IFNγ 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.

journal of neuroinflammation

IFN-gamma signaling in the central nervous system controls the course of experimental autoimmune encephalomyelitis independently of the localization and composition of inflammatory foci