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Title: Prevention of ischemic brain injury by treatment with the membrane penetrating apoptosis inhibitor, TAT-BH4
Authors: 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
First Published: 15-Apr-2009
Publisher: Landes Bioscience
Citation: Cell Cycle, 2009, 8 (8), pp. 1271-1278.
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.
DOI Link: 10.4161/cc.8.8.8301
ISSN: 1538-4101
Type: Article
Rights: This paper was published as Cell Cycle, 2009, 8 (8), pp. 1271-1278. It is available from DOI: 10.4161/cc.8.8.8301
Description: Metadata only entry
Appears in Collections:Published Articles, MRC Toxicology Unit

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