Alterations of the ceramide metabolism in the peri-infarct cortex are independent of the sphingomyelinase pathway and not influenced by the acid sphingomyelinase inhibitor fluoxetine

  • Ceramides induce important intracellular signaling pathways, modulating proliferation, migration, apoptosis, and inflammation. However, the relevance of the ceramide metabolism in the reconvalescence phase after stroke is unclear. Besides its well-known property as a selective serotonin reuptake inhibitor, fluoxetine has been reported to inhibit the acid sphingomyelinase (ASM), a key regulator of ceramide levels which derives ceramide from sphingomyelin. Furthermore, fluoxetine has shown therapeutic potential in a randomized controlled rehabilitation trial in stroke patients. Our aim was to investigate and modulate ceramide concentrations in the peri-infarct cortex, whose morphological and functional properties correlate with long-term functional outcome in stroke. We show that certain ceramide species are modulated after experimental stroke and that these changes do not result from alterations of ASM activity, but rather from nontranscriptional induction of the ceramide de novo pathway. Unexpectedly, although reducing lesion size, fluoxetine did not improve functional outcome in our model and had no significant influence on ASM activity or the concentration of ceramides. The ceramide metabolism could emerge as a potential therapeutic target in the reconvalescence phase after stroke, as its accumulation in the peri-infarct cortex potentially influences membrane functions as well as signaling events in the tissue essential for neurological recovery.

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Author:Robert BrunkhorstGND, Felix Friedländer, Nerea Ferreirós BouzasORCiDGND, Stephanie SchwalmGND, Alexander Koch, Georgios Grammatikos, Stefan Tönnes, Christian FörchORCiDGND, Josef Martin PfeilschifterGND, Waltraud PfeilschifterORCiDGND
Pubmed Id:
Parent Title (English):Neural plasticity
Place of publication:New York, NY
Contributor(s):Michael S. Beattie
Document Type:Article
Year of Completion:2015
Year of first Publication:2015
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2019/08/05
Issue:Art. 503079
Page Number:11
First Page:1
Last Page:10
Copyright © 2015 R. Brunkhorst et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 3.0