Erythropoietin prevents neuronal apoptosis after cerebral ischemia and metabolic stress

DOI Web Site 被引用文献23件
  • Anna-Leena Sirén
    Max Planck Institute for Experimental Medicine and Departments of Neurology and Psychiatry, and Department of Clinical Pharmacology, Georg August University, 37075 Goettingen, Germany; Department of Molecular Biochemistry and Pharmacology, Mario Negri Institute for Pharmacological Research, Milan, Italy 20157; Department of Clinical Pharmacology, Eberhard Karls University, 72074 Tuebingen, Germany; Department of Molecular Neurobiochemistry, Ruhr University, 44780 Bochum, Germany; and The...
  • Maddalena Fratelli
    Max Planck Institute for Experimental Medicine and Departments of Neurology and Psychiatry, and Department of Clinical Pharmacology, Georg August University, 37075 Goettingen, Germany; Department of Molecular Biochemistry and Pharmacology, Mario Negri Institute for Pharmacological Research, Milan, Italy 20157; Department of Clinical Pharmacology, Eberhard Karls University, 72074 Tuebingen, Germany; Department of Molecular Neurobiochemistry, Ruhr University, 44780 Bochum, Germany; and The...
  • Michael Brines
    Max Planck Institute for Experimental Medicine and Departments of Neurology and Psychiatry, and Department of Clinical Pharmacology, Georg August University, 37075 Goettingen, Germany; Department of Molecular Biochemistry and Pharmacology, Mario Negri Institute for Pharmacological Research, Milan, Italy 20157; Department of Clinical Pharmacology, Eberhard Karls University, 72074 Tuebingen, Germany; Department of Molecular Neurobiochemistry, Ruhr University, 44780 Bochum, Germany; and The...
  • Christoph Goemans
    Max Planck Institute for Experimental Medicine and Departments of Neurology and Psychiatry, and Department of Clinical Pharmacology, Georg August University, 37075 Goettingen, Germany; Department of Molecular Biochemistry and Pharmacology, Mario Negri Institute for Pharmacological Research, Milan, Italy 20157; Department of Clinical Pharmacology, Eberhard Karls University, 72074 Tuebingen, Germany; Department of Molecular Neurobiochemistry, Ruhr University, 44780 Bochum, Germany; and The...
  • Simona Casagrande
    Max Planck Institute for Experimental Medicine and Departments of Neurology and Psychiatry, and Department of Clinical Pharmacology, Georg August University, 37075 Goettingen, Germany; Department of Molecular Biochemistry and Pharmacology, Mario Negri Institute for Pharmacological Research, Milan, Italy 20157; Department of Clinical Pharmacology, Eberhard Karls University, 72074 Tuebingen, Germany; Department of Molecular Neurobiochemistry, Ruhr University, 44780 Bochum, Germany; and The...
  • Piotr Lewczuk
    Max Planck Institute for Experimental Medicine and Departments of Neurology and Psychiatry, and Department of Clinical Pharmacology, Georg August University, 37075 Goettingen, Germany; Department of Molecular Biochemistry and Pharmacology, Mario Negri Institute for Pharmacological Research, Milan, Italy 20157; Department of Clinical Pharmacology, Eberhard Karls University, 72074 Tuebingen, Germany; Department of Molecular Neurobiochemistry, Ruhr University, 44780 Bochum, Germany; and The...
  • Sonja Keenan
    Max Planck Institute for Experimental Medicine and Departments of Neurology and Psychiatry, and Department of Clinical Pharmacology, Georg August University, 37075 Goettingen, Germany; Department of Molecular Biochemistry and Pharmacology, Mario Negri Institute for Pharmacological Research, Milan, Italy 20157; Department of Clinical Pharmacology, Eberhard Karls University, 72074 Tuebingen, Germany; Department of Molecular Neurobiochemistry, Ruhr University, 44780 Bochum, Germany; and The...
  • Christoph Gleiter
    Max Planck Institute for Experimental Medicine and Departments of Neurology and Psychiatry, and Department of Clinical Pharmacology, Georg August University, 37075 Goettingen, Germany; Department of Molecular Biochemistry and Pharmacology, Mario Negri Institute for Pharmacological Research, Milan, Italy 20157; Department of Clinical Pharmacology, Eberhard Karls University, 72074 Tuebingen, Germany; Department of Molecular Neurobiochemistry, Ruhr University, 44780 Bochum, Germany; and The...
  • Claudio Pasquali
    Max Planck Institute for Experimental Medicine and Departments of Neurology and Psychiatry, and Department of Clinical Pharmacology, Georg August University, 37075 Goettingen, Germany; Department of Molecular Biochemistry and Pharmacology, Mario Negri Institute for Pharmacological Research, Milan, Italy 20157; Department of Clinical Pharmacology, Eberhard Karls University, 72074 Tuebingen, Germany; Department of Molecular Neurobiochemistry, Ruhr University, 44780 Bochum, Germany; and The...
  • Annalisa Capobianco
    Max Planck Institute for Experimental Medicine and Departments of Neurology and Psychiatry, and Department of Clinical Pharmacology, Georg August University, 37075 Goettingen, Germany; Department of Molecular Biochemistry and Pharmacology, Mario Negri Institute for Pharmacological Research, Milan, Italy 20157; Department of Clinical Pharmacology, Eberhard Karls University, 72074 Tuebingen, Germany; Department of Molecular Neurobiochemistry, Ruhr University, 44780 Bochum, Germany; and The...
  • Tiziana Mennini
    Max Planck Institute for Experimental Medicine and Departments of Neurology and Psychiatry, and Department of Clinical Pharmacology, Georg August University, 37075 Goettingen, Germany; Department of Molecular Biochemistry and Pharmacology, Mario Negri Institute for Pharmacological Research, Milan, Italy 20157; Department of Clinical Pharmacology, Eberhard Karls University, 72074 Tuebingen, Germany; Department of Molecular Neurobiochemistry, Ruhr University, 44780 Bochum, Germany; and The...
  • Rolf Heumann
    Max Planck Institute for Experimental Medicine and Departments of Neurology and Psychiatry, and Department of Clinical Pharmacology, Georg August University, 37075 Goettingen, Germany; Department of Molecular Biochemistry and Pharmacology, Mario Negri Institute for Pharmacological Research, Milan, Italy 20157; Department of Clinical Pharmacology, Eberhard Karls University, 72074 Tuebingen, Germany; Department of Molecular Neurobiochemistry, Ruhr University, 44780 Bochum, Germany; and The...
  • Anthony Cerami
    Max Planck Institute for Experimental Medicine and Departments of Neurology and Psychiatry, and Department of Clinical Pharmacology, Georg August University, 37075 Goettingen, Germany; Department of Molecular Biochemistry and Pharmacology, Mario Negri Institute for Pharmacological Research, Milan, Italy 20157; Department of Clinical Pharmacology, Eberhard Karls University, 72074 Tuebingen, Germany; Department of Molecular Neurobiochemistry, Ruhr University, 44780 Bochum, Germany; and The...
  • Hannelore Ehrenreich
    Max Planck Institute for Experimental Medicine and Departments of Neurology and Psychiatry, and Department of Clinical Pharmacology, Georg August University, 37075 Goettingen, Germany; Department of Molecular Biochemistry and Pharmacology, Mario Negri Institute for Pharmacological Research, Milan, Italy 20157; Department of Clinical Pharmacology, Eberhard Karls University, 72074 Tuebingen, Germany; Department of Molecular Neurobiochemistry, Ruhr University, 44780 Bochum, Germany; and The...
  • Pietro Ghezzi
    Max Planck Institute for Experimental Medicine and Departments of Neurology and Psychiatry, and Department of Clinical Pharmacology, Georg August University, 37075 Goettingen, Germany; Department of Molecular Biochemistry and Pharmacology, Mario Negri Institute for Pharmacological Research, Milan, Italy 20157; Department of Clinical Pharmacology, Eberhard Karls University, 72074 Tuebingen, Germany; Department of Molecular Neurobiochemistry, Ruhr University, 44780 Bochum, Germany; and The...

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<jats:p>Erythropoietin (EPO) promotes neuronal survival after hypoxia and other metabolic insults by largely unknown mechanisms. Apoptosis and necrosis have been proposed as mechanisms of cellular demise, and either could be the target of actions of EPO. This study evaluates whether antiapoptotic mechanisms can account for the neuroprotective actions of EPO. Systemic administration of EPO (5,000 units/kg of body weight, i.p.) after middle-cerebral artery occlusion in rats dramatically reduces the volume of infarction 24 h later, in concert with an almost complete reduction in the number of terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling of neurons within the ischemic penumbra. In both pure and mixed neuronal cultures, EPO (0.1–10 units/ml) also inhibits apoptosis induced by serum deprivation or kainic acid exposure. Protection requires pretreatment, consistent with the induction of a gene expression program, and is sustained for 3 days without the continued presence of EPO. EPO (0.3 units/ml) also protects hippocampal neurons against hypoxia-induced neuronal death through activation of extracellular signal-regulated kinases and protein kinase Akt-1/protein kinase B. The action of EPO is not limited to directly promoting cell survival, as EPO is trophic but not mitogenic in cultured neuronal cells. These data suggest that inhibition of neuronal apoptosis underlies short latency protective effects of EPO after cerebral ischemia and other brain injuries. The neurotrophic actions suggest there may be longer-latency effects as well. Evaluation of EPO, a compound established as clinically safe, as neuroprotective therapy in acute brain injury is further supported.</jats:p>

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