1. ¹Department of Neurology, University of Heidelberg, Heidelberg, Germany
2. ²Forschungszentrum Karlsruhe, Institute of Toxicology and Genetics, Heidelberg, Germany
3. ³Axaron Bioscience, Heidelberg, Germany

Correspondence: Dr Markus Schwaninger, Department of Neurology, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany. E-mail: markus.schwaninger@med.uni-heidelberg.de

^*Current address: Department of Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

^†Current address: Department of Immunology, Institute of Molecular Biotechnology, Beutenberg Str. 11, 07745 Jena, Germany.

Received 19 April 2004; Revised 28 June 2004; Accepted 11 August 2004.

Abstract

The transcription factor NF-B is a key regulator of inflammation and cell survival. NF-B is activated by cerebral ischemia in neurons and glia, but its function is controversial. To inhibit NF-B selectively in neurons and glial cells, we have generated transgenic mice that express the IB superrepressor (IB mutated at serine-32 and serine-36, IB-SR) under transcriptional control of the neuron-specific enolase (NSE) and the glial fibrillary acidic protein (GFAP) promoter, respectively. In primary cortical neurons of NSE-IB-SR mice, NF-B activity was partially inhibited. To assess NF-B activity in vivo after permanent middle cerebral artery occlusion (MCAO), we measured the expression of NF-B target genes by real-time polymerase chain reaction (PCR). The induction of c-myc and transforming growth factor-2 by cerebral ischemia was inhibited by neuronal expression of IB-SR, whereas induction of GFAP by MCAO was reduced by astrocytic expression of IB-SR. Neuronal, but not astrocytic, expression of the NF-B inhibitor reduced both infarct size and cell death 48 hours after permanent MCAO. In summary, the data show that NF-B is activated in neurons and astrocytes during cerebral ischemia and that NF-B activation in neurons contributes to the ischemic damage.