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.