Prevention of ischemic brain injury by treatment with the membrane penetrating apoptosis inhibitor, TAT-BH4

Sandra Donnini, Raffaella Solito, Martina Monti, Walter Balduini, Silvia Carloni, Mauro Cimino, Edward T W Bampton, Lucia G P Pinon, Pierluigi Nicotera, Philip E. Thorpe, Marina Ziche

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

In acute thromboembolic stroke, neurological damage is due to ischemia-induced apoptotic death of neuronal cells and the surrounding vascular network. Here, we demonstrate that the BH4 domain of the anti-apoptotic protein, Bcl-xL, attached to the membrane transport peptide, TAT, reduces stroke injury after intracerebroventricular infusion into immature rats subjected to carotid artery ligation and additional exposure to hypoxia. The injected TAT-BH4 entered neuron bodies, maintained brain architecture, protected neuronal and endothelial cells from apoptosis and promoted neuronal stem cell recruitment. In vitro, TAT-BH4 enhanced the survival of endothelial cells exposed to H2O2, increased neuronal differentiation, and induced axonal remodelling of adult neuronal stem cells. These findings indicate that TAT-BH4 administration protects against acute hypoxia/ischemia injury in the brain by preventing endothelial and neuron cell apoptosis and by inducing neuronal plasticity.

Original languageEnglish (US)
Pages (from-to)1271-1278
Number of pages8
JournalCell Cycle
Volume8
Issue number8
DOIs
StatePublished - Apr 15 2009

Keywords

  • Apoptosis
  • Endothelial cells
  • Neuron cells
  • Neuronal progenitor cells
  • TAT-BH4

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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    Donnini, S., Solito, R., Monti, M., Balduini, W., Carloni, S., Cimino, M., Bampton, E. T. W., Pinon, L. G. P., Nicotera, P., Thorpe, P. E., & Ziche, M. (2009). Prevention of ischemic brain injury by treatment with the membrane penetrating apoptosis inhibitor, TAT-BH4. Cell Cycle, 8(8), 1271-1278. https://doi.org/10.4161/cc.8.8.8301