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• W2044001092 startingPage "308" @default.
• W2044001092 abstract "The mechanisms of cell death and the progressive degeneration of neural tissue following traumatic brain injury (TBI) have come under intense investigation. However, the complex interactions among the evolving pathologies in multiple cell types obscure the causal relationships between the initial effects of the mechanical trauma at the cellular level and the long-term dysfunction and neuronal death. We used an in vitro model of neuronal injury to study the mechanisms of cell death in response to a well-defined mechanical insult and found that the majority of dead cells were apoptotic. We have previously reported that promotion of membrane repair acutely with the non-ionic surfactant poloxamer 188 (P188) restored cell viability to control values at 24 h postinjury. Here, we showed that P188 significantly inhibits apoptosis and prevents necrosis. We also examined the role of mitogen-activated protein kinases (MAPKs) in cell death. There was a rapid, transient activation of extracellular signal-regulated kinases, c-Jun N-terminal kinase, and p38s after mechanical insult. Of these, activation of the proapoptotic p38 was the greatest. Treatment with P188 inhibited p38 activation; however, direct inhibition of p38 by SB203580, which selectively inhibits the activity of the p38 MAPK, provided only partial inhibition of apoptosis and had no effect on necrosis. These data suggest that multiple signaling pathways may be involved in the long-term response of neurons to mechanical injury. Furthermore, that the membrane resealing action of P188 provides such significant protection from both necrosis and apoptosis suggests that acute membrane damage due to trauma is a critical precipitating event that is upstream of the many signaling cascades contributing to the subsequent pathology." @default.
• W2044001092 created "2016-06-24" @default.
• W2044001092 creator A5023431483 @default.
• W2044001092 creator A5036563549 @default.
• W2044001092 creator A5046332939 @default.
• W2044001092 creator A5059614418 @default.
• W2044001092 date "2005-12-21" @default.
• W2044001092 modified "2023-10-06" @default.
• W2044001092 title "Mechanisms of cell death and neuroprotection by poloxamer 188 after mechanical trauma" @default.
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• W2044001092 doi "https://doi.org/10.1096/fj.05-4024fje" @default.
• W2044001092 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/16371428" @default.
• W2044001092 hasPublicationYear "2005" @default.
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