Differential effects on glial activation by a direct versus an indirect thrombin inhibitor

M. Natalia Marangoni, David Braun, Annie Situ, Ana L. Moyano, Sergey Kalinin, Paul Polak, Maria I. Givogri, Douglas L. Feinstein

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Thrombin is a potent regulator of brain function in health and disease, modulating glial activation and brain inflammation. Thrombin inhibitors, several of which are in clinical use as anti-coagulants, can reduce thrombin-dependent neuroinflammation in pathological conditions. However, their effects in a healthy CNS are largely unknown. In adult healthy mice, we compared the effects of treatment by the direct thrombin inhibitor dabigatran etexilate (DE), to those of warfarin, which acts by preventing vitamin K recycling essential for coagulation. After 4 weeks, warfarin increased both astrocyte GFAP and microglia Iba-1 staining throughout the CNS; whereas DE reduced expression of both markers. Warfarin, but not DE, reduced sulfatide levels; and warfarin showed longer lasting changes in cerebellar gene expression. DE also reduced glial activation in a mouse model of Alzheimer's disease, although no changes in amyloid plaque burden were observed. These results suggest that treatment with direct thrombin inhibitors may be preferable to those agents which reduce vitamin K levels and have the potential to increase glial activation.

Original languageEnglish
Pages (from-to)159-168
Number of pages10
JournalJournal of Neuroimmunology
Volume297
DOIs
StatePublished - Aug 15 2016

Bibliographical note

Publisher Copyright:
© 2015.

Keywords

  • Astrocyte
  • Dabigatran
  • Microglia
  • Sulfatides
  • Vitamin K
  • Warfarin

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Neurology
  • Clinical Neurology

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