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- W2080669600 abstract "Pluronic F-68, an 80% hydrophilic member of the Pluronic family of polyethylene-polypropylene-polyethylene tri-block copolymers, protects non-neuronal cells from traumatic injuries and rescues hippocampal neurons from excitotoxic and oxidative insults. F-68 interacts directly with lipid membranes and restores membrane function after direct membrane damage. Here, we demonstrate the efficacy of Pluronic F-68 in rescuing rat hippocampal neurons from apoptosis after oxygen–glucose deprivation (OGD). OGD progressively decreased neuronal survival over 48 h in a severity-dependent manner, the majority of cell death occurring after 12 h after OGD. Administration of F-68 for 48 h after OGD rescued neurons from death in a dose-dependent manner. At its optimal concentration (30 μm), F-68 rescued all neurons that would have died after the first hour after OGD. This level of rescue persisted when F-68 administration was delayed 12 h after OGD. F-68 did not alter electrophysiological parameters controlling excitability, NMDA receptor-activated currents, or NMDA-induced increases in cytosolic calcium concentrations. However, F-68 treatment prevented phosphatidylserine externalization, caspase activation, loss of mitochondrial membrane potential, and BAX translocation to mitochondria, indicating that F-68 alters apoptotic mechanisms early in the intrinsic pathway of apoptosis. The profound neuronal rescue provided by F-68 after OGD and the high level of efficacy with delayed administration indicate that Pluronic copolymers may provide a novel, membrane-targeted approach to rescuing neurons after brain ischemia. The ability of membrane-active agents to block apoptosis suggests that membranes or their lipid components play prominent roles in injury-induced apoptosis." @default.
- W2080669600 created "2016-06-24" @default.
- W2080669600 creator A5007736608 @default.
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- W2080669600 creator A5028324921 @default.
- W2080669600 creator A5040541373 @default.
- W2080669600 creator A5041636491 @default.
- W2080669600 date "2013-07-24" @default.
- W2080669600 modified "2023-10-18" @default.
- W2080669600 title "The Membrane-Active Tri-Block Copolymer Pluronic F-68 Profoundly Rescues Rat Hippocampal Neurons from Oxygen-Glucose Deprivation-Induced Death through Early Inhibition of Apoptosis" @default.
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- W2080669600 doi "https://doi.org/10.1523/jneurosci.5731-12.2013" @default.
- W2080669600 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3721839" @default.
- W2080669600 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/23884935" @default.
- W2080669600 hasPublicationYear "2013" @default.
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