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Decreased brain damage and curtailed inflammation in transcription factor CCAAT/enhancer binding protein β knockout mice following transient focal cerebral ischemia
Author(s) -
Kapadia Ramya,
Tureyen Kudret,
Bowen Kellie K.,
Kalluri Haviryaji,
Johnson Peter F.,
Vemuganti Raghu
Publication year - 2006
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2006.04056.x
Subject(s) - inflammation , ccaat enhancer binding proteins , knockout mouse , microglia , ischemia , transcription factor , biology , endocrinology , medicine , immunology , biochemistry , gene , nuclear protein , receptor
CCAAT/enhancer binding protein β (C/EBPβ) is a leucine‐zipper transcription factor that regulates cell growth and differentiation in mammals. Expression of many pro‐inflammatory genes including the cytokine interleukin‐6 is known to be controlled by C/EBPβ. We report that focal cerebral ischemia induced by transient middle cerebral artery occlusion (MCAO) significantly increases C/EBPβ gene expression in mouse brain at between 6 and 72 h of reperfusion. To understand the functional significance of C/EBPβ in postischemic inflammation and brain damage, we induced transient MCAO in cohorts of adult C/EBPβ null mice and their wild‐type littermates. At 3 days of reperfusion following transient MCAO, C/EBPβ null mice showed significantly smaller infarcts, reduced neurological deficits, decreased terminal deoxynucleotidyl transferase‐mediated dUTP nick‐end labeling‐positive cells, decreased intercellular adhesion molecule 1 (ICAM1) immunopositive vessels, decreased extravasated neutrophils and fewer activated microglia/macrophages, compared with their wild‐type littermates. Furthermore, GeneChip analysis showed that postischemic induction of many transcripts known to promote inflammation and neuronal damage was less pronounced in the brains of C/EBPβ –/– mice compared with C/EBPβ +/+ mice. These results suggest a significant role for C/EBPβ in postischemic inflammation and brain damage.