CCAAT/enhancer binding protein β deficiency provides cerebral protection following excitotoxic injury

The CCAAT/enhancer-binding protein beta (C/EBP beta, also known as CEBPB) was first identified as a regulator of differentiation and inflammatory processes in adipose tissue and liver. Although C/EBP beta was initially implicated in synaptic plasticity, its function in the brain remains largely unknown. We have previously shown that C/EBP beta regulates the expression of genes involved in inflammatory processes and brain injury. Here, we have demonstrated that the expression of C/EBP beta is notably increased in the hippocampus in a murine model of excitotoxicity. Mice lacking C/EBP beta showed a reduced inflammatory response after kainic acid injection, and exhibited a dramatic reduction in pyramidal cell loss in the CA1 and CA3 subfields of the hippocampus. These data reveal an essential function for C/EBP beta in the pathways leading to excitotoxicity-mediated damage and suggest that inhibitors of this transcription factor should be evaluated as possible neuroprotective therapeutic agents.