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Oxidative stress after intracranial hemorrhage
Author(s) -
Wakisaka Yoshinobu,
Miller Jordan D,
Lund Donald D,
Chu Yi,
Baumbach Gary L,
Faraci Frank M,
Heistad Donald D
Publication year - 2007
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.21.5.a396-c
Subject(s) - oxidative stress , medicine
Mechanisms of brain injury after intracranial hemorrhage (ICH) are not clear. We tested the hypothesis that extravascular blood activates NADPH oxidase and increases superoxide in a mouse model of ICH. Four μl of autologous blood or artificial cerebrospinal fluid (aCSF) were injected into the striatum of anesthetized C57BL/6 mice. Twenty hours later, superoxide levels were measured in homogenized brain. Superoxide levels, using the tiron‐inhibitable fraction of lucigenin‐enhanced chemiluminescence, were increased following blood injection (blood 0.15±0.04 vs aCSF 0.05±0.01 RLU/sec/μg protein, p<0.05) (mean±SE). Using dihydroethidium in brain slices, superoxide was increased in brain parenchyma around the hematoma. NADPH oxidase activity in brain homogenates was greater in the blood injected hemisphere (blood 22±2 vs aCSF 8±1 RLU/sec/μg protein, p<0.001) (mean±SE). Quantitative real‐time PCR demonstrated no change in expression of the catalytic subunits of the NADPH oxidase (Nox1, Nox2, and Nox4). Diphenyliodonium, an inhibitor of NADPH oxidase activity, markedly reduced superoxide levels in both blood and aCSF injected brain. Thus, increases in superoxide may be due to increased activity, but not altered expression, of NADPH oxidese. Collectively, these data suggest that extravascular blood increases superoxide perhaps through activation of NADPH oxidase.