Metabolomic Analyses of Brain Tissue in Sepsis Induced by Cecal Ligation Reveal Specific Redox Alterations-Protective Effects of the Oxygen Radical Scavenger Edaravone.

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Bibtex

@article{5e8c117e330c4f20952058f9b7c344e9,
title = "Metabolomic Analyses of Brain Tissue in Sepsis Induced by Cecal Ligation Reveal Specific Redox Alterations-Protective Effects of the Oxygen Radical Scavenger Edaravone.",
abstract = "The pathophysiology of sepsis-associated encephalopathy (SAE) is complex and remains incompletely elucidated. Dysregulated reactive oxygen species (ROS) production and mitochondrial-mediated necrotic-apoptotic pathway have been proposed as part of the pathogenesis. The present study aimed at analyzing the preventive effect of the free radical scavenger edaravone on sepsis-induced brain alterations. Sepsis was induced by cecal ligation and puncture (CLP) and the mice were divided into three groups-CLP vehicle (CLPV), CLP and edaravone (MCI-186, 3-methyl-1-phenyl-2-pyrazolin-5-one) (CLPE), and sham-operated (Sham). Mice in CLPV and CLPE were injected with saline or edaravone intraperitoneally at a dose of 10 mg/kg twice daily. The treatments were initiated 4 days prior to the surgical procedure. Mortality, histological changes, electron microscopy (EM), and expression of Bcl-2 family genes (Bcl-2 and Bax) were analyzed in selected brain regions. CLPE showed significant improvement in survival compared with CLPV 18 h postinduction of sepsis (P < 0.05). At the same time point, pathohistological analysis also showed marked reduction of neuronal cell death in both parietal cortex and hippocampus in the CLPE (P < 0.05). RT-PCR and immunoblotting directed at the Bcl-2 family revealed increased Bax mRNA levels in hippocampus at 12 h in CLPV as well as an increased Bax/Bcl-2 protein ratio, changes that were significantly suppressed in CLPE. In conclusion, our study suggests that sepsis induced by cecal ligation alters cerebral redox status and supports a proapoptotic phenotype. The free radical scavenger edavarone reduces mortality of septic mice and protects against sepsis-induced neuronal cell death.",
author = "Naomi Hara and Miyuki Chijiiwa and Miki Yara and Yusuke Ishida and Yukihiko Ogiwara and Masato Inazu and Masahiko Kuroda and Michael Karlsson and Fredrik Sj{\"o}vall and Eskil Elmer and Hiroyuki Uchino",
year = "2015",
doi = "10.1097/SHK.0000000000000465",
language = "English",
volume = "44",
pages = "578--584",
journal = "Shock",
issn = "1540-0514",
publisher = "Lippincott Williams & Wilkins",
number = "6",

}