TY  - JOUR
A1  - Brunkhorst, Robert
A1  - Friedländer, Felix
A1  - Ferreirós Bouzas, Nerea
A1  - Schwalm, Stephanie
A1  - Koch, Alexander
A1  - Grammatikos, Georgios
A1  - Tönnes, Stefan W.
A1  - Förch, Christian
A1  - Pfeilschifter, Josef
A1  - Pfeilschifter, Waltraud
T1  - 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
T2  - Neural plasticity
N2  - 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.
Y1  - 2015
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/50664
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-506643
SN  - 1687-5443
SN  - 2090-5904
N1  - 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.
VL  - 23
IS  - Art. 503079
SP  - 1
EP  - 10
PB  - Hindawi
CY  - New York, NY
ER  -