Cellular and Molecular Neurobiology

, Volume 23, Issue 4–5, pp 539–550 | Cite as

Transforming Growth Factor-β and Ischemic Brain Injury

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

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.

TGF-β cerebral ischemia molecular 

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Copyright information

© Plenum Publishing Corporation 2003

Authors and Affiliations

  • Alain Buisson
    • 1
  • Sylvain Lesne
    • 1
  • Fabian Docagne
    • 1
  • Carine Ali
    • 1
  • Olivier Nicole
    • 1
  • Eric T. MacKenzie
    • 1
  • Denis Vivien
    • 1
  1. 1.Feder, Centre CYCERONUniversit1é de CAEN, UMR CNRSCaen CedexFrance

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