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• W4213302273 endingPage "147837" @default.
• W4213302273 startingPage "147837" @default.
• W4213302273 abstract "Periventricular leukomalacia (PVL), the dominant cerebral white matter injury disease, is induced by hypoxia–ischemia and inflammation in premature infants. The activation of A2B adenosine receptor (A2BAR) is shown to involve into inflammation, ischemia, and other typical stress reactions, but its exact function in PVL has not been clarified. We gained initial insight from PVL mouse model (P9) by the induction of hypoxia–ischemia with right carotid ligation followed by exposure to hypoxia and intraperitoneal (i.p.) injection of Lipopolysaccharide (LPS). The results showed that treatment of PSB-603, an A2BAR selective antagonist, greatly ameliorated cerebral ischemic injury by increasing body weights, reducing infarct volume, brain injury, inflammation and contributing to long-term learning memory functional recovery of the PVL mice. Meanwhile, PSB-603 treatment suppressed neurons apoptosis as characterized by reducing of Caspase-3 level, inhibited microglia activation and attenuated hypomyelination through promoting MBP expression and oligodendrocytes differentiation. A2BAR inhibition also augmented PKC expression, the activity of PKC downstream signaling molecules were then explored. Erk expression and Creb phosphorylation exhibited upregulation in PSB-603 treatment group compared with the control group. Hypoxia Inducible Factor-1α (HIF-1α), a direct target of hypoxia, which is a key regulator of adenosine signaling by binding to the A2BAR promoter to induce expression of A2BAR, was shown to be decreased by PSB-603. Taken together, A2BAR inhibition can ameliorate hypoxic-ischemic injury in PVL mice maybe through PKC/Erk/Creb/HIF-1α signaling pathway." @default.
• W4213302273 created "2022-02-24" @default.
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• W4213302273 date "2022-05-01" @default.
• W4213302273 modified "2023-10-01" @default.
• W4213302273 title "A2B adenosine receptor inhibition ameliorates hypoxic-ischemic injury in neonatal mice via PKC/Erk/Creb/HIF-1α signaling pathway" @default.
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• W4213302273 doi "https://doi.org/10.1016/j.brainres.2022.147837" @default.
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