{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T17:26:15Z","timestamp":1791307575969,"version":"4.3.1"},"reference-count":46,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2011,6,14]],"date-time":"2011-06-14T00:00:00Z","timestamp":1308009600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2011,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective:<\/jats:title><jats:p>Perinatal brain injury is a major cause of neurodevelopmental handicaps. Multiple pathways of oxidant stress, inflammation, and excitotoxicity lead to cell damage and death, including caspase\u2010dependent apoptosis. Caspase\u20102 (Casp2; Nedd\u20102, Ich\u20101) is a developmentally regulated initiator caspase, which poorly cleaves other caspases but can initiate mitochondrial outer membrane permeabilization. We have investigated if Casp2 could mediate perinatal ischemic brain damage.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods:<\/jats:title><jats:p>Casp2 expression in human neonatal brains and developmental patterns in rats and mice were evaluated. Casp2\u2010deficient (<jats:italic>Casp2<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>), wild\u2010type (WT), and heterozygous (<jats:italic>Casp2<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup>) newborn C57BL\/6 mice were subjected to hypoxia\u2010ischemia (unilateral carotid occlusion + exposure to 10% oxygen for 50 minutes) or intracerebral injection of the excitotoxic N\u2010methyl\u2010<jats:sc>D<\/jats:sc>\u2010aspartate\u2010receptor agonist ibotenate. In addition, Casp2 specific siRNAs were preinjected into the brain of WT newborn mice 24 hours before ibotenate treatment. Brain tissues were examined by immunohistochemical staining (cresyl violet, MAP2, NF68, Casp2, Casp3) and Western blotting. Lesion volumes and injury in the cortical plates and white matter were quantified together with activated Casp3.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results:<\/jats:title><jats:p>Casp2 is highly expressed in the neonatal brain. Casp2\u2010deficient mice subjected to hypoxia\u2010ischemia at postnatal day 9 present significantly lower cerebral infarction, reduced white matter injury, and reduced Casp3 activation in the thalamus and hippocampus. Both <jats:italic>Casp2<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice and siRNA\u2010administered WT mice conferred reduction of gray and white matter injury after excitotoxic insult at postnatal day 5. Casp3 activation was also found reduced in <jats:italic>Casp2<\/jats:italic>\u2010deficient mice subjected to excitotoxicity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation:<\/jats:title><jats:p>These data suggest for the first time a role of Casp2 in neonatal brain damage. ANN NEUROL 2011;<\/jats:p><\/jats:sec>","DOI":"10.1002\/ana.22431","type":"journal-article","created":{"date-parts":[[2011,3,28]],"date-time":"2011-03-28T18:42:10Z","timestamp":1301337730000},"page":"781-789","source":"Crossref","is-referenced-by-count":63,"title":["Genetic inhibition of caspase\u20102 reduces hypoxic\u2010ischemic and excitotoxic neonatal brain injury"],"prefix":"10.1002","volume":"70","author":[{"given":"Ylva","family":"Carlsson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leslie","family":"Schwendimann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regina","family":"Vontell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine 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