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Phosphoinositide 3-kinase-gamma expression is upregulated in brain microglia and contributes to ischemia-induced microglial activation in acute experimental stroke |
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| Authors: | Rong Jin Zifang Song Daniel P Deasis Anil Nanda Guohong Li |
| Institution: | a Department of Neurosurgery, Vascular Biology & Stroke Research Laboratory, Louisiana State University Health Sciences Center, Shreveport, LA, USA b Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA, USA c Louisiana State University Health Sciences Center, Shreveport, LA, USA d IMBA, Institute for Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria |
| Abstract: | Microglia, the resident microphages of the CNS, are rapidly activated after ischemic stroke. Inhibition of microglial activation may protect the brain by attenuating blood-brain barrier damage and neuronal apoptosis after ischemic stroke. However, the mechanisms by which microglia is activated following cerebral ischemia is not well defined. In this study, we investigated the expression of PI3Kγ in normal and ischemic brains and found that PI3Kγ mRNA and protein are constitutively expressed in normal brain microvessels, but significantly upregulated in postischemic brain primarily in activated microglia following cerebral ischemia. In vitro, the expression of PI3Kγ mRNA and protein was verified in mouse brain endothelial and microglial cell lines. Importantly, absence of PI3Kγ blocked the early microglia activation (at 4 h) and subsequent expansion (at 24-72 h) in PI3Kγ knockout mice. The results suggest that PI3Kγ is an ischemia-responsive gene in brain microglia and contributes to ischemia-induced microglial activation and expansion. |
| Keywords: | Phosphoinositide 3-kinase-gamma Ischemia Microglia Endothelial cells Stroke |
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