Cell-death agents in stroke

The real title of the article is: 
N-terminally cleaved Bcl-x_L mediates ischemia-induced neuronal death

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Transient global ischemia in rats induces delayed death of hippocampal CA1 neurons. Early events include caspase activation, cleavage of anti-death Bcl-2 family proteins and large mitochondrial channel activity. However, whether these events have a causal role in ischemia-induced neuronal death is unclear. We found that the Bcl-2 and Bcl-x_L inhibitor ABT-737, which enhances death of tumor cells, protected rats against neuronal death in a clinically relevant model of brain ischemia. Bcl-x_L is prominently expressed in adult neurons and can be cleaved by caspases to generate a pro-death fragment, ΔN-Bcl-x_L. We found that ABT-737 administered before or after ischemia inhibited ΔN-Bcl-x_L–induced mitochondrial channel activity and neuronal death. To establish a causal role for ΔN-Bcl-x_L, we generated knock-in mice expressing a caspase-resistant form of Bcl-x_L. The knock-in mice exhibited markedly reduced mitochondrial channel activity and reduced vulnerability to ischemia-induced neuronal death. These findings suggest that truncated Bcl-x_L could be a potentially important therapeutic target in ischemic brain injury.