We have shown that S1P selectively constricts cerebral,
but not peripheral arteries via S1P3 receptors
(Salomone et al, 2003). The brain is one of the organs containing the
highest concentration of S1P, and we have shown that one of the S1P-synthesizing
enzymes, sphingosine kinase 2, is the predominant isoform in neurons.
In addition to constricting brain blood vessels, S1P also stimulates
proliferation of vascular cells (endothelial cells and smooth muscle
cells, and protects them from ischemia induced cells death. We hypothesize
that in the normal brain or under pathological conditions such as ischemia,
brain cells release significant amounts of S1P that controls vascular tone,
protects from ischemia-induced cell death, and induces repair mechanisms.
All three actions are particularly important in the context of cerebral
We are currently investigating the role of the immune response in the beneficial effects of fingolimod in rodent models of stroke.
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