Transforming growth factor-beta and ischemic brain injury

Cell Mol Neurobiol. 2003 Oct;23(4-5):539-50. doi: 10.1023/a:1025072013107.


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-beta1 (TGF-beta1) 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-beta1 against ischemia-induced neuronal death. In vitro, TGF-beta1 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-beta1 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-beta signaling or TGF-beta1-modulated genes could be good targets for the development of new therapeutic strategies for stroke in man.

Publication types

  • Review

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / physiology
  • Brain Infarction / drug therapy
  • Brain Infarction / genetics
  • Brain Infarction / metabolism*
  • Brain Ischemia / drug therapy
  • Brain Ischemia / genetics
  • Brain Ischemia / metabolism*
  • Carrier Proteins / metabolism
  • Humans
  • Mitogen-Activated Protein Kinases / metabolism
  • Neuroprotective Agents / metabolism*
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use
  • Plasminogen Activator Inhibitor 1 / metabolism
  • Transforming Growth Factor beta / metabolism*
  • Transforming Growth Factor beta / pharmacology
  • Transforming Growth Factor beta / therapeutic use
  • Transforming Growth Factor beta1
  • bcl-Associated Death Protein


  • BAD protein, human
  • Carrier Proteins
  • Neuroprotective Agents
  • Plasminogen Activator Inhibitor 1
  • TGFB1 protein, human
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • bcl-Associated Death Protein
  • Mitogen-Activated Protein Kinases