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• W2898634013 startingPage "2828" @default.
• W2898634013 abstract "The inflammatory response mediated by microglia plays a critical role in the progression of ischemic stroke. Phosphoinositide 3-kinase gamma (PI3Kγ) has been implicated in multiple inflammatory and autoimmune diseases, making it a promising target for therapeutic intervention. The aim of this study was to evaluate the efficacy of 8e, a hydrogen sulfide (H2S) releasing derivative of 3-n-butylphthalide (NBP), on brain damage and PI3Kγ signaling following cerebral ischemia injury. 8e significantly reduced sensorimotor deficits, focal infarction, brain edema and neural apoptosis at 72 h after transient middle cerebral artery occlusion (tMCAO). The NOX2 isoform of the NADPH oxidase family is considered a major enzymatic source of superoxide. We found that the release of superoxide, together with the expression of NOX2 subunits p47phox, p-p47phox, and the upstream PI3Kγ/AKT signaling were all down-regulated by 8e, both in the penumbral region of the rat brain and in the primary cultured microglia subjected to oxygen-glucose deprivation (OGD). With the use of siRNA and pharmacological inhibitors, we further demonstrated that 8e regulates the formation of superoxide in activated microglia through the PI3Kγ/AKT/NOX2 signaling pathway and subsequently prevents neuronal death in neighboring neurons. Our experimental data indicate that 8e is a potential candidate for the treatment of ischemic stroke and PI3Kγ-mediated neuroinflammation." @default.
• W2898634013 created "2018-11-09" @default.
• W2898634013 creator A5008614366 @default.
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• W2898634013 creator A5073434350 @default.
• W2898634013 creator A5087099599 @default.
• W2898634013 date "2018-10-31" @default.
• W2898634013 modified "2023-09-26" @default.
• W2898634013 title "8e Protects against Acute Cerebral Ischemia by Inhibition of PI3Kγ-Mediated Superoxide Generation in Microglia" @default.
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• W2898634013 doi "https://doi.org/10.3390/molecules23112828" @default.
• W2898634013 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6278485" @default.
• W2898634013 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30384445" @default.
• W2898634013 hasPublicationYear "2018" @default.

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