Decreased brain damage and curtailed inflammation in transcription factor CCAAT/enhancer binding protein β knockout mice following transient focal cerebral ischemia

Authors


Address correspondence and reprint requests to Raghu Vemuganti, PhD, Department of Neurological Surgery, University of Wisconsin, K4/8 (Mail stop code CSC-8660), 600 Highland Avenue, Madison, WI 53792, USA. E-mail: vemugant@neurosurg.wisc.edu

Abstract

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.

Ancillary