NOS2 and brain ischemia: Following cellular stimulation with inflammatory cytokines, iNOS can be rapidly induced to mediate NO production,48 and iNOS inhibition is known to reduced infarct size following cerebral ischemia, thus reducing the associated brain damage.49, 50 Our results suggest that Sphk1/S1P may play a role in regulating iNOS activity after IRI, potentially altering tissue inflammation without promoting angiogenesis.