Transforming growth factor-β and ischemic brain injury

Alain Buisson, Sylvain Lesne, Fabian Docagne, Carine Ali, Olivier Nicole, Eric T. MacKenzie, Denis Vivien

Research output: Contribution to journalReview article

73 Scopus citations

Abstract

1. Necrosis and apoptosis are the two fundamental hallmarks of neuronal death in stroke. Nevertheless, thrombolysis, by using the recombinant serine protease t-PA, remains until now the only approved treatment of stroke in man. 2. Over the last years, the cytokine termed Transforming Growth Factor-β1 (TGF-β1) has been found to be strongly up-regulated in the central nervous system following ischemia-induced brain damage. 3. Recent studies have shown a neuroprotective activity of TGF-β1 against ischemia-induced neuronal death. In vitro, TGF-β1 protects neurons against excitotoxicity by inhibiting the t-PA-potentiated NMDA-induced neuronal death through a mechanism involving the up-regulation of the type-1 plasminogen activator inhibitor (PAI-1) in astrocytes. 4. In addition, TGF-β1 has been recently characterized as an antiapoptotic factor in a model of staurosporine-induced neuronal death through a mechanism involving activation of the extracellular signal-regulated kinase 1/2 (Erk1/2) and a concomitant increase phosphorylation of the antiapoptotic protein Bad. 5. Altogether, these observations suggest that either TGF-β signaling or TGF-β1-modulated genes could be good targets for the development of new therapeutic strategies for stroke in man.

Original languageEnglish (US)
Pages (from-to)539-550
Number of pages12
JournalCellular and Molecular Neurobiology
Volume23
Issue number4-5
DOIs
StatePublished - Oct 2003

Keywords

  • Cerebral ischemia
  • Molecular
  • TGF-β

Fingerprint Dive into the research topics of 'Transforming growth factor-β and ischemic brain injury'. Together they form a unique fingerprint.

  • Cite this

    Buisson, A., Lesne, S., Docagne, F., Ali, C., Nicole, O., MacKenzie, E. T., & Vivien, D. (2003). Transforming growth factor-β and ischemic brain injury. Cellular and Molecular Neurobiology, 23(4-5), 539-550. https://doi.org/10.1023/A:1025072013107