Article Document Academic Article Information Content Entity Journal Article Continuant Continuant Entity Entity Generically Dependent Continuant 2025-05-08T02:48:56 RDF description of Intranasal delivery of caspase-9 inhibitor reduces caspase-6-dependent axon/neuron loss and improves neurological function after stroke - http://repository.healthpartners.com/individual/document-rn19504 Intranasal delivery of caspase-9 inhibitor reduces caspase-6-dependent axon/neuron loss and improves neurological function after stroke Cardiovascular Diseases 10.1523/jneurosci.0698-11.2011 Drugs and Drug Therapy Animal Studies 24 23716 31 <p>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 provided neurofunctional protection and established caspase-6 as its downstream target. The temporal and spatial pattern of expression demonstrates that neuronal caspase-9 activity induces caspase-6 activation, mediating axonal loss by 12 hpr followed by neuronal death within 24 hpr. Collectively, these results support selective inhibition of these specific caspases as an effective therapeutic strategy for stroke.<p> Intranasal Administration Nervous System Diseases 14568 public Journal of Neuroscience Stroke document-rn19504 2022-02-21T22:48:57.408-06:00