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Intranasal Delivery of Caspase-9 Inhibitor Reduces Caspase-6-Dependent Axon/Neuron Loss and Improves Neurological Function after Stroke.

J Neurosci.. 2011-06;  31(24):8894 - 8904
Nsikan Akpan, Esther Serrano-Saiz, Brad E. Zacharia, Marc L. Otten, Andrew F. Ducruet, Scott J. Snipas, Wen Liu, Jennifer Velloza, Greg Cohen, Sergeyi A. Sosunov, William H. Frey, II, Guy S. Salvesen, E. Sander Connolly, Jr, and Carol M. Troy. Department of Pathology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
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摘要

Despite extensive research to develop an effective neuroprotective strategy for the treatment of ischemic stroke, therapeutic options remain limited. Although caspase-dependent death is thought to play a prominent role in neuronal injury, direct evidence of active initiator caspases in stroke and the functional relevance of this activity have not previously been shown. Using an unbiased caspase-trapping technique in vivo, we isolated active caspase-9 from ischemic rat brain within 1 h of reperfusion. Pathogenic relevance of active caspase-9 was shown by intranasal delivery of a novel cell membrane-penetrating highly specific inhibitor for active caspase-9 at 4 h postreperfusion (hpr). Caspase-9 inhibition provi... More

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