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NF-κB is activated and promotes cell death in focal cerebral ischemia

Nature Medicine volume 5, pages 554–559 (1999)Cite this article

Abstract

The transcription factor NF-κB is a regulator of cell death or survival. To investigate the role of NF-κB in neuronal cell death, we studied its activation in a rodent model of stroke. In the ischemic hemisphere, NF-κB was activated, as determined by increased expression of an NF-κB-driven reporter transgene, nuclear translocation of NF-κB in neurons and enhanced DNA binding of NF-κB subunits RelA and p50. In p50 knockout mice, ischemic damage was significantly reduced. This indicates a cell death-promoting role of NF-κB in focal ischemia. NF-κB may provide a new pharmacological target in neurologic disease.

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Figure 1: Transcriptional activity of NF-κB is increased in focal cerebral ischemia.
Figure 2: Increase of NF-κB activity is confined to distinct brain areas.
Figure 3: Activated NF-κB localizes to neurons.
Figure 4: Increased DNA binding of p50 and RelA in cerebral ischemia.
Figure 5: Ischemic damage is reduced in mice deficient in the p50 subunit of NF-κB.

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Acknowledgements

Acknowledgment We thank P. Chan for help with establishing the filament model in mice; and S. Prinz, N. Attigah, and Y. Xu for their help at various stages of the project. This work was supported by a grant of the DFG to M.S.

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Authors and Affiliations

  1. Department of Neurology, University of Heidelberg Im Neuenheimer Feld 400, Heidelberg, 69120, Germany

    Armin Schneider, Ana Martin-Villalba & Markus Schwaninger

  2. Department of Neuroscience, BASF-LYNX Bioscience AG Im Neuenheimer Feld 515, Heidelberg, 69120, Germany

    Armin Schneider

  3. Department of Physiology, Im Neuenheimer Feld 326, Heidelberg, 69120, Germany

    Ana Martin-Villalba

  4. Forschungszentrum Karlsruhe, Institute of Genetics , PO Box 3640, Karlsruhe, 76021, Germany

    Falk Weih

  5. Institute of Radiobiology and Cell Research, Versbacherstr. 5, Würzburg, 97078, Germany

    Johannes Vogel

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Schneider, A., Martin-Villalba, A., Weih, F. et al. NF-κB is activated and promotes cell death in focal cerebral ischemia . Nat Med 5, 554–559 (1999). https://doi.org/10.1038/8432

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