{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T23:31:00Z","timestamp":1769815860954,"version":"3.49.0"},"reference-count":75,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2014,1,3]],"date-time":"2014-01-03T00:00:00Z","timestamp":1388707200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["International Journal of Stroke"],"published-print":{"date-parts":[[2014,7]]},"abstract":"<jats:sec><jats:title>Background and Aims<\/jats:title><jats:p> Hypothermia provides neuroprotection after cardiac arrest, hypoxic-ischemic encephalopathy, and in animal models of ischemic stroke. However, as drug development for stroke has been beset by translational failure, we sought additional evidence that hypothermia protects human neurons against ischemic injury. <\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p> Human embryonic stem cells were cultured and differentiated to provide a source of neurons expressing \u03b2 III tubulin, microtubule-associated protein 2, and the Neuronal Nuclei antigen. Oxygen deprivation, oxygen-glucose deprivation, and H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>-induced oxidative stress were used to induce relevant injury. <\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p> Hypothermia to 33\u00b0C protected these human neurons against H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>-induced oxidative stress reducing lactate dehydrogenase release and Terminal deoxynucleotidyl transferase dUTP nick end labeling-staining by 53% ( P \u2264 0\u00b70001; 95% confidence interval 34\u00b78\u201371\u00b704) and 42% ( P \u2264 0\u00b70001; 95% confidence interval 27\u00b75\u201356\u00b76), respectively, after 24 h in culture. Hypothermia provided similar protection against oxygen-glucose deprivation (42%, P \u2264 0\u00b7001, 95% confidence interval 18\u00b73\u201371\u00b73 and 26%, P \u2264 0\u00b7001; 95% confidence interval 12\u00b74\u201352\u00b72, respectively) but provided no protection against oxygen deprivation alone. Protection (21%) persisted against H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>-induced oxidative stress even when hypothermia was initiated six-hours after onset of injury ( P \u2264 0\u00b705; 95% confidence interval 0\u00b757\u201343\u00b71). <\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p> We conclude that hypothermia protects stem cell-derived human neurons against insults relevant to stroke over a clinically relevant time frame. Protection against H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>-induced injury and combined oxygen and glucose deprivation but not against oxygen deprivation alone suggests an interaction in which protection benefits from reduction in available glucose under some but not all circumstances. <\/jats:p><\/jats:sec>","DOI":"10.1111\/ijs.12224","type":"journal-article","created":{"date-parts":[[2014,1,3]],"date-time":"2014-01-03T06:51:00Z","timestamp":1388731860000},"page":"544-552","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":24,"title":["Hypothermia Protects Human Neurons"],"prefix":"10.1177","volume":"9","author":[{"given":"Ana","family":"Antonic","sequence":"first","affiliation":[{"name":"Florey Institute of Neuroscience and Mental Health, Heidelberg, Vic, Australia"},{"name":"Department of Medicine, University of Melbourne, Heidelberg, Vic, 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