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dc.contributor.authorFink, K
dc.contributor.authorZhu, JM
dc.contributor.authorNamura, S
dc.contributor.authorShimizu-Sasamata, M
dc.contributor.authorEndres, M
dc.contributor.authorMa, JY
dc.contributor.authorDalkara, T
dc.contributor.authorYuan, JY
dc.contributor.authorMoskowitz, MA
dc.date.accessioned2019-12-10T11:25:46Z
dc.date.available2019-12-10T11:25:46Z
dc.date.issued1998
dc.identifier.issn0271-678X
dc.identifier.urihttps://doi.org/10.1097/00004647-199810000-00003
dc.identifier.urihttp://hdl.handle.net/11655/15722
dc.description.abstractApoptotic cell death is prominent in neurodegenerative disorders, such as Alzheimer's disease and Huntington's disease? and is found in cerebral ischemia. Using a murine model of delayed cell death, we determined that cleavage of zDEVD-amino-4-trifluoromethyl coumarin (zDEVD-afc) in brain homogenate, a measure of caspase activation, increased initially 9 hours after brief (30 minutes) middle cerebral artery occlusion along with caspase-3p20 immunoreactive cleavage product as determined by immunoblotting. zDEVD-afc cleavage activity was blocked by pretreatment or posttreatment with the caspase-inhibitor N-benzyloxycarbonyl-Asp(OMe)-Glu(OMe)-Val-Asp(OMe)-fluoromethyl-ketone (zDEVD-fmk), and ischemic damage was reduced when the drug was injected up to 9 hours after reperfusion. The protection was long lasting (21 days). Hence, the period before caspase activation defined the therapeutic opportunity for this neuroprotective agent after mild ischemic brain injury. Prolonged protection after caspase inhibition plus the extended treatment window may be especially relevant to the treatment of neurodegenerative disorders.
dc.language.isoen
dc.publisherSage Publications Inc
dc.relation.isversionof10.1097/00004647-199810000-00003
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectEndocrinology & Metabolism
dc.subjectHematology
dc.subjectNeurosciences & Neurology
dc.titleProlonged Therapeutic Window for Ischemic Brain Damage Caused by Delayed Caspase Activation
dc.typeinfo:eu-repo/semantics/article
dc.typeinfo:eu-repo/semantics/publishedVersion
dc.relation.journalJournal Of Cerebral Blood Flow And Metabolism
dc.contributor.departmentNöroloji
dc.identifier.volume18
dc.identifier.issue10
dc.identifier.startpage1071
dc.identifier.endpage1076
dc.description.indexWoS
dc.description.indexScopus


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