Phosphoinositide 3-Kinase y Restrains Neurotoxic Effects of Microglia After Focal XXXX .

@entity268 @entity4798 @entity2806 @entity63 @entity75 @entity2500 @entity19 @entity26 @entity1235 @entity9675 @entity413
UNASSIGNED: Phosphoinositide 3-kinase y (PI3Ky) is linked to neuroinflammation and phagocytosis. This study was conducted to elucidate conjectural differences of lipid kinase-dependent and kinase-independent functions of PI3Ky in the evolvement of @entity75 induced by focal @entity2806 /reperfusion. Therefore, PI3Ky wild-type, knockout, and kinase-dead @entity19 were subjected to @entity2500 followed by reperfusion. Tissue damage and cellular composition were assessed by immunohistochemical stainings. In addition, microglial cells derived from respective @entity19 genotypes were used for analysis of PI3Ky effects on phagocytic activity, @entity1235 release, and @entity268 content under conditions of @entity26 / @entity413 deprivation and recovery. @entity4798 was more pronounced in PI3Ky-knockout @entity19 compared to wild-type and kinase-dead @entity19 48  h after reperfusion. Immunohistochemical analyses revealed a reduced amount of galectin-3/ @entity9675 -positive microglial cells indicating that activated phagocytosis was reduced in ischemic brains of knockout @entity19 . Cell culture studies disclosed enhanced metalloproteinase-9 secretion in supernatants derived from microglia of PI3Ky-deficient @entity19 after 2-h @entity26 / @entity413 deprivation and 48-h recovery. Furthermore, PI3Ky-deficient microglial cells showed a failed phagocytic activation throughout the observed recovery period. Lastly, PI3Ky-deficient microglia exhibited strongly increased @entity268 levels in comparison with wild-type microglia or cells expressing kinase-dead PI3Ky after @entity26 / @entity413 deprivation and recovery. Our data suggest PI3Ky kinase activity-independent control of @entity268 phosphodiesterase as a crucial mediator of microglial @entity268 regulation, @entity1235 expression, and phagocytic activity following focal @entity2806 /recirculation. The suppressive effect of PI3Ky on @entity268 levels appears critical for the restriction of @entity63 -induced immune cell functions and in turn tissue damage.
