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

Cell cycle (Georgetown, Tex.) 2009 Apr 15

filter terms:

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-x(L), 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 H(2)O(2), 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.

Citation

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. Prevention of ischemic brain injury by treatment with the membrane penetrating apoptosis inhibitor, TAT-BH4. Cell cycle (Georgetown, Tex.). 2009 Apr 15;8(8):1271-8