Sphingosine kinase 1 mediates neuroinflammation following cerebral ischemia.

Sphingosine kinase 1 mediates neuroinflammation following cerebral ischemia. Exp Neurol. 2015 Mar 19; Authors: Zheng S, Wei S, Wang X, Xu Y, Xiao Y, Liu H, Jia J, Cheng J Abstract Sphingosine kinases (Sphks) are the rate-limiting kinases in the generation of sphingosine-1-phosphate, which is a well-established intracellular pro-survival lipid mediator. Sphk2 has been reported to be protective following experimental stroke. We investigated the role of Sphk1 in cerebral ischemia using a mouse middle cerebral artery occlusion (MCAO) model and an in vitro glucose-oxygen deprivation (OGD) model. Sphk expression and activity were assessed in the ischemic brain with quantitative PCR (qPCR), western blot, immunohistochemistry and enzyme-linked immunosorbent assay (ELISA). Pharmacological and gene knockdown approaches were utilized to investigate the effects of Sphk1 on stroke outcomes. The expression of Sphk1 but not that of Sphk2 was rapidly induced in the cortical penumbra over 96 hours after MCAO, and the microglia were one of the major cellular sources of Sphk1 induction. Consistently, Sphk activity was enhanced in the cortical penumbra. In contrast to the protective role of Sphk2, pharmacological inhibition and cortical knockdown of Sphk1 reduced infarction at 24 and 96 hours after reperfusion. Additionally, the Sphk1 inhibitor improved the neurological deficits at 96 hours after reperfusion. Mechanistically, Sphk1 inhibition and knockd...
Source: Experimental Neurology - Category: Neurology Authors: Tags: Exp Neurol Source Type: research