Neuroprotective effect of Fn14 deficiency is associated with induction of the granulocyte-colony stimulating factor (G-CSF) pathway in experimental stroke and enhanced by a pathogenic human antiphospholipid antibody

Katrin Frauenknecht; Panagiotis Bargiotas; Henrike Bauer; Philipp von Landenberg; Markus Schwaninger; Clemens Sommer

doi:10.1016/j.jneuroim.2010.05.043

Neuroprotective effect of Fn14 deficiency is associated with induction of the granulocyte-colony stimulating factor (G-CSF) pathway in experimental stroke and enhanced by a pathogenic human antiphospholipid antibody

J Neuroimmunol. 2010 Oct 8;227(1-2):1-9. doi: 10.1016/j.jneuroim.2010.05.043. Epub 2010 Jun 16.

Authors

Katrin Frauenknecht¹, Panagiotis Bargiotas, Henrike Bauer, Philipp von Landenberg, Markus Schwaninger, Clemens Sommer

Affiliation

¹ Department of Neuropathology, University Medical Center of the Johannes Gutenberg University Mainz, D-55131 Mainz, Germany. [email protected]

PMID: 20557950
DOI: 10.1016/j.jneuroim.2010.05.043

Abstract

Using a transgenic mouse model of ischemic stroke we checked for a possible interaction of antiphospholipid antibodies (aPL) which often cause thromboses as well as central nervous system (CNS) involvement under non-thrombotic conditions and the TWEAK/Fn14 pathway known to be adversely involved in inflammatory and ischemic brain disease. After 7 days, infarct volumes were reduced in Fn14 deficient mice and were further decreased by aPL treatment. This was associated with strongest increase of the endogenous neuroprotective G-CSF/G-CSF receptor system. This unexpected beneficial action of aPL is an example for a non-thrombogenic action and the double-edged nature of aPL.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antibodies, Antiphospholipid / adverse effects
Antibodies, Antiphospholipid / therapeutic use*
Brain Ischemia / metabolism*
Brain Ischemia / pathology
Brain Ischemia / prevention & control*
Disease Models, Animal*
Granulocyte Colony-Stimulating Factor / biosynthesis*
Granulocyte Colony-Stimulating Factor / physiology
Humans
Inflammation Mediators / metabolism
Inflammation Mediators / physiology
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Random Allocation
Receptors, Granulocyte Colony-Stimulating Factor / biosynthesis
Receptors, Granulocyte Colony-Stimulating Factor / physiology
Receptors, Tumor Necrosis Factor / deficiency*
Receptors, Tumor Necrosis Factor / physiology
Signal Transduction / genetics
TWEAK Receptor

Substances

Antibodies, Antiphospholipid
Inflammation Mediators
Receptors, Granulocyte Colony-Stimulating Factor
Receptors, Tumor Necrosis Factor
TNFRSF12A protein, human
TWEAK Receptor
Tnfrsf12a protein, mouse
Granulocyte Colony-Stimulating Factor