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Histopathological changes in septic mouse brain: effect of the free‐radical scavenger edaravone
Author(s) -
Yokoo Hiroki,
Hattori Yuichi
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1004.12
Subject(s) - edaravone , proinflammatory cytokine , nitrotyrosine , sepsis , evans blue , tumor necrosis factor alpha , pathology , blood–brain barrier , immunostaining , chemistry , free radical scavenger , inflammation , medicine , immunology , pharmacology , central nervous system , endocrinology , immunohistochemistry , nitric oxide synthase , biochemistry , oxidative stress , enzyme
Despite the fact that neuronal dysfunction can occur in the course of sepsis, sepsis‐associated histopathological changes in the brain are poorly understood. We found that mRNA expression levels of proinflammatory cytokines, including tumor necrosis factor‐alpha, interleukin‐1beta, and interleukin‐6, were up‐regulated in brain tissues from mice with cecal ligation and puncture‐induced sepsis, but to a much lesser extent when compared with those in peripheral tissues such as lungs. Importantly, blood‐brain barrier permeability was greatly increased in septic mice, as determined by the measurement of sodium fluorescence or Evans Blue content. This was associated with increased immunostaining for nitrotyrosine, a stable biomarker of reactive nitrogen species, in cerebral vessels. Light and electron microscopic examination of septic mouse brain showed the presence of many neuronal cells that appeared deformed, shrunken, and densely‐stained, which were mitigated by treatment with edaravone, a free‐radical scavenger. We thus suggest that the histopathological derangement of neuronal cells in septic mouse brain is associated with enhanced generation of free‐radical species.