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 language | English (US) |
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Pages (from-to) | 1271-1278 |
Number of pages | 8 |
Journal | Cell Cycle |
Volume | 8 |
Issue number | 8 |
DOIs | |
State | Published - Apr 15 2009 |
Keywords
- Apoptosis
- Endothelial cells
- Neuron cells
- Neuronal progenitor cells
- TAT-BH4
ASJC Scopus subject areas
- Molecular Biology
- Developmental Biology
- Cell Biology