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 Citations (Scopus)

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
StatePublished - Apr 15 2009

Fingerprint

Brain Injuries
Neuronal Plasticity
Endothelial Cells
Apoptosis
Membranes
Ischemia
Stroke
Intraventricular Infusions
Neurons
Apoptosis Regulatory Proteins
Adult Stem Cells
Carotid Arteries
Ligation
Blood Vessels
Cell Death
Stem Cells
Therapeutics
Peptides
Wounds and Injuries
Brain

Keywords

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

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

Cite this

Donnini, S., Solito, R., Monti, M., Balduini, W., Carloni, S., Cimino, M., ... Ziche, M. (2009). Prevention of ischemic brain injury by treatment with the membrane penetrating apoptosis inhibitor, TAT-BH4. Cell Cycle, 8(8), 1271-1278.

Prevention of ischemic brain injury by treatment with the membrane penetrating apoptosis inhibitor, TAT-BH4. / Donnini, Sandra; Solito, Raffaella; Monti, Martina; Balduini, Walter; Carloni, Silvia; Cimino, Mauro; Bampton, Edward T W; Pinon, Lucia G P; Nicotera, Pierluigi; Thorpe, Philip E.; Ziche, Marina.

In: Cell Cycle, Vol. 8, No. 8, 15.04.2009, p. 1271-1278.

Research output: Contribution to journalArticle

Donnini, S, Solito, R, Monti, M, Balduini, W, Carloni, S, Cimino, M, Bampton, ETW, Pinon, LGP, Nicotera, P, Thorpe, PE & Ziche, M 2009, 'Prevention of ischemic brain injury by treatment with the membrane penetrating apoptosis inhibitor, TAT-BH4', Cell Cycle, vol. 8, no. 8, pp. 1271-1278.
Donnini S, Solito R, Monti M, Balduini W, Carloni S, Cimino M et al. Prevention of ischemic brain injury by treatment with the membrane penetrating apoptosis inhibitor, TAT-BH4. Cell Cycle. 2009 Apr 15;8(8):1271-1278.
Donnini, Sandra ; Solito, Raffaella ; Monti, Martina ; Balduini, Walter ; Carloni, Silvia ; Cimino, Mauro ; Bampton, Edward T W ; Pinon, Lucia G P ; Nicotera, Pierluigi ; Thorpe, Philip E. ; Ziche, Marina. / Prevention of ischemic brain injury by treatment with the membrane penetrating apoptosis inhibitor, TAT-BH4. In: Cell Cycle. 2009 ; Vol. 8, No. 8. pp. 1271-1278.
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