Report

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

Volume 8, Issue 8   April 15, 2009
Pages 1271 - 1278
http://dx.doi.org/10.4161/cc.8.8.8301
Authors: 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 and Marina Ziche

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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.

Received: January 28, 2009; Accepted: February 26, 2009

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