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57th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN)

German Society for Neuropathology and Neuroanatomy

12. - 15.09.2012, Erlangen

57th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN)

Decreased astrocytic NF-κB activation under laquinimodprevents cuprizone-induced demyelination

Meeting Abstract

  • presenting/speaker Christiane Wegner - University of Goettingen, Department of Neuropathology, Göttingen, Germany
  • Ramona Pförtner - University of Goettingen, Department of Neuropathology, Göttingen, Germany
  • Nadine Kramann - University of Goettingen, Department of Neuropathology, Göttingen, Germany
  • Uwe Hanisch - University of Goettingen, Department of Neuropathology, Göttingen, Germany
  • Gareth John - Mount Sinai School of Medicine, New York, United States
  • Wolfgang Brück - University of Goettingen, Department of Neuropathology, Göttingen, Germany

Deutsche Gesellschaft für Neuropathologie und Neuroanatomie. 57th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN). Erlangen, 12.-15.09.2012. Düsseldorf: German Medical Science GMS Publishing House; 2012. Doc12dgnnPP2.8

DOI: 10.3205/12dgnn044, URN: urn:nbn:de:0183-12dgnn0449

Published: September 11, 2012

© 2012 Wegner et al.
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Outline

Text

Background: Laquinimod (LAQ) is an oral drug that reduces relapse rate, brain atrophy and disability progression in multiple sclerosis. LAQ down-modulates inflammation in the periphery, but it is not clear whether it exerts effects within the central nervous system (CNS). Cuprizone induced-demyelination takes place in the near absence of T cells with an intact blood-brain barrier. With this animal model it is possible to study the effect of LAQ on CNS cells without the influence of the peripheral immune system.

Aim: To investigate the impact of LAQ on CNS-resident cells, we examined the effects of LAQ on cuprizone-induced demyelination in mice in vivo and on primary CNS cells in vitro.

Methods: Demyelination, inflammation, axonal damage and glial pathology were evaluated in LAQ-treated wild type mice after cuprizone challenge. Using primary cells we tested for effects of LAQ on cytokine secretion and NF-κB activation in astrocytes and microglia.

Results: LAQ prevented cuprizone-induced demyelination, microglial activation, axonal transections, reactive gliosis and oligodendroglial apoptoses in mice. LAQ significantly reduced pro-inflammatory factors in stimulated astrocytes, but not in microglia. LAQ markedly reduced astrocytic, but not microglial, NF-κB activation evidenced by NF-κB reporter assay. LAQ also decreased astrocytic NF-κB activation in cuprizone-treated mice.

Conclusions: Our data indicate that LAQ prevents cuprizone-induced demyelination by attenuating astrocytic NF-κB activation. These effects are CNS-intrinsic and not mediated by peripheral immune cells. Modulation of astrocytic activation may represent a novel protective means of restricting tissue damage in demyelinating diseases.