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Transgenic mutant ICE mice (n = 11) and wild-type littermates (n = 9) were subjected to 3 h of middle cerebral artery occlusion followed by 24 h of reperfusion. Cerebral infarcts and brain swelling were reduced by 44% and 46%, respectively. Neurological deficits were also significantly reduced. Regional CBF, blood pressure, core temperature, and heart rate did not differ between groups when measured for up to 1 h after reperfusion. Increases in immunoreactive IL-1\u03b2 levels, observed in ischemic wild-type brain at 30 min after reperfusion, were 77% lower in the mutant strain, indicating that proIL-1\u03b2 cleavage is inhibited in the mutants. DNA fragmentation was reduced in the mutants 6 and 24 h after reperfusion. Hence, endogenous expression of an ICE inhibitor confers resistance to cerebral ischemia and brain swelling. Our results indicate that down-regulation of ICE expression might provide a useful therapeutic target in cerebral ischemia.<\/jats:p>","DOI":"10.1097\/00004647-199704000-00002","type":"journal-article","created":{"date-parts":[[2004,9,1]],"date-time":"2004-09-01T22:49:44Z","timestamp":1094078984000},"page":"370-375","source":"Crossref","is-referenced-by-count":190,"title":["Attenuation of Transient Focal Cerebral Ischemic Injury in Transgenic Mice Expressing a Mutant ICE Inhibitory Protein"],"prefix":"10.1177","volume":"17","author":[{"given":"Hideaki","family":"Hara","sequence":"first","affiliation":[{"name":"Stroke and Neurovascular Regulation, Neurosurgical Service and Neurology Department, Massachusetts General Hospital, Harvard Medical School, Charlestown"}]},{"given":"Klaus","family":"Fink","sequence":"additional","affiliation":[{"name":"Stroke and Neurovascular Regulation, Neurosurgical Service and Neurology Department, Massachusetts General Hospital, Harvard Medical School, 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