{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T00:06:53Z","timestamp":1792714013711,"version":"4.5.0"},"reference-count":14,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2015,1]]},"abstract":"<jats:sec>\n            <jats:title>Background and Purpose\u2014<\/jats:title>\n            <jats:p>In infants with moderate to severe neonatal encephalopathy, whole-body cooling at 33\u00b0C to 34\u00b0C for 72 hours is standard care with a number needed to treat to prevent a adverse outcome of 6 to 7. The precise brain temperature providing optimal neuroprotection is unknown.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods\u2014<\/jats:title>\n            <jats:p>After a quantified global cerebral hypoxic-ischemic insult, 28 piglets aged &lt;24 hours were randomized (each group, n=7) to (1) normothermia (38.5\u00b0C throughout) or whole-body cooling 2 to 26 hours after insult to (2) 35\u00b0C, (3) 33.5\u00b0C, or (4) 30\u00b0C. At 48 hours after hypoxia-ischemia, delayed cell death (terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling and cleaved caspase 3) and microglial ramification (ionized calcium-binding adapter molecule 1) were evaluated.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results\u2014<\/jats:title>\n            <jats:p>\n              At 48 hours after hypoxia-ischemia, substantial cerebral injury was found in the normothermia and 30\u00b0C hypothermia groups. However, with 35\u00b0C and 33.5\u00b0C cooling, a clear reduction in delayed cell death and microglial activation was observed in most brain regions (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.05), with no differences between 35\u00b0C and 33.5\u00b0C cooling groups. A protective pattern was observed, with U-shaped temperature dependence in delayed cell death in periventricular white matter, caudate nucleus, putamen, hippocampus, and thalamus. A microglial activation pattern was also seen, with inverted U-shaped temperature dependence in periventricular white matter, caudate nucleus, internal capsule, and hippocampus (all\n              <jats:italic>P<\/jats:italic>\n              &lt;0.05).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>Cooling to 35\u00b0C (an absolute drop of 3.5\u00b0C as in therapeutic hypothermia protocols) or to 33.5\u00b0C provided protection in most brain regions after a cerebral hypoxic-ischemic insult in the newborn piglet. Although the relatively wide therapeutic range of a 3.5\u00b0C to 5\u00b0C drop in temperature reassured, overcooling (an 8.5\u00b0C drop) was clearly detrimental in some brain regions.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/strokeaha.114.007330","type":"journal-article","created":{"date-parts":[[2014,11,26]],"date-time":"2014-11-26T04:46:59Z","timestamp":1416977219000},"page":"275-278","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":91,"title":["Brain Cell Death Is Reduced With Cooling by 3.5\u00b0C to 5\u00b0C but Increased With Cooling by 8.5\u00b0C in a Piglet Asphyxia Model"],"prefix":"10.1161","volume":"46","author":[{"given":"Daniel","family":"Alonso-Alconada","sequence":"first","affiliation":[{"name":"From the Institute for Women\u2019s Health, University College London, London, United Kingdom (D.A.-A., K.D.B., M.C., S.D.F., A.K., J.H., E.R.-F., M.H., K.B., D.K., N.J.R.); Medical Physics and Bio-engineering, University College London Hospitals NHS Foundation Trust, London, United Kingdom (A.B., E.C.); Centre for the Developing Brain, King\u2019s College London, London, United Kingdom (B.F., P.G.); and Department of Brain Repair and Rehabilitation, Institute for Neurology, Queen Square, London, United..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin D.","family":"Broad","sequence":"additional","affiliation":[{"name":"From the Institute for Women\u2019s Health, University College London, London, United Kingdom (D.A.-A., K.D.B., M.C., S.D.F., A.K., J.H., E.R.-F., M.H., K.B., D.K., N.J.R.); Medical Physics and Bio-engineering, University College London Hospitals NHS Foundation Trust, London, United Kingdom (A.B., E.C.); Centre for the Developing Brain, King\u2019s College London, London, United Kingdom (B.F., P.G.); and Department of Brain Repair and Rehabilitation, Institute for Neurology, Queen Square, London, United..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Bainbridge","sequence":"additional","affiliation":[{"name":"From the Institute for Women\u2019s Health, University College London, London, United Kingdom (D.A.-A., K.D.B., M.C., S.D.F., A.K., J.H., E.R.-F., M.H., K.B., D.K., N.J.R.); Medical Physics and Bio-engineering, University College London Hospitals NHS Foundation Trust, London, United Kingdom (A.B., E.C.); Centre for the Developing Brain, King\u2019s College London, London, United Kingdom (B.F., P.G.); and Department of Brain Repair and Rehabilitation, Institute for Neurology, Queen Square, London, United..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manigandan","family":"Chandrasekaran","sequence":"additional","affiliation":[{"name":"From the Institute for Women\u2019s Health, University College London, London, United Kingdom (D.A.-A., K.D.B., M.C., S.D.F., A.K., J.H., E.R.-F., M.H., K.B., D.K., N.J.R.); Medical Physics and Bio-engineering, University College London Hospitals NHS Foundation Trust, London, United Kingdom (A.B., E.C.); Centre for the Developing Brain, King\u2019s College London, London, United Kingdom (B.F., P.G.); and Department of Brain Repair and Rehabilitation, Institute for Neurology, Queen Square, London, United..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart D.","family":"Faulkner","sequence":"additional","affiliation":[{"name":"From the Institute for Women\u2019s Health, University College London, London, United Kingdom (D.A.-A., K.D.B., M.C., S.D.F., A.K., J.H., E.R.-F., M.H., K.B., D.K., N.J.R.); Medical Physics and Bio-engineering, University College London Hospitals NHS Foundation Trust, London, United Kingdom (A.B., E.C.); Centre for the Developing Brain, King\u2019s College London, London, United Kingdom (B.F., P.G.); and Department of Brain Repair and Rehabilitation, Institute for Neurology, Queen Square, London, United..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1ron","family":"Kerenyi","sequence":"additional","affiliation":[{"name":"From the Institute for Women\u2019s Health, University College London, London, United Kingdom (D.A.-A., K.D.B., M.C., S.D.F., A.K., J.H., E.R.-F., M.H., K.B., D.K., N.J.R.); Medical Physics and Bio-engineering, University College London Hospitals NHS Foundation Trust, London, United Kingdom (A.B., E.C.); Centre for the Developing Brain, King\u2019s College London, London, United Kingdom (B.F., P.G.); and Department of Brain Repair and Rehabilitation, Institute for Neurology, Queen Square, London, United..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"Hassell","sequence":"additional","affiliation":[{"name":"From the Institute for Women\u2019s Health, University College London, London, United Kingdom (D.A.-A., K.D.B., M.C., S.D.F., A.K., J.H., E.R.-F., M.H., K.B., D.K., N.J.R.); Medical Physics and Bio-engineering, University College London Hospitals NHS Foundation Trust, London, United Kingdom (A.B., E.C.); Centre for the Developing Brain, King\u2019s College London, London, United Kingdom (B.F., P.G.); and Department of Brain Repair and Rehabilitation, Institute for Neurology, Queen Square, London, United..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eridan","family":"Rocha-Ferreira","sequence":"additional","affiliation":[{"name":"From the Institute for Women\u2019s Health, University College London, London, United Kingdom (D.A.-A., K.D.B., M.C., S.D.F., A.K., J.H., E.R.-F., M.H., K.B., D.K., N.J.R.); Medical Physics and Bio-engineering, University College London Hospitals NHS Foundation Trust, London, United Kingdom (A.B., E.C.); Centre for the Developing Brain, King\u2019s College London, London, United Kingdom (B.F., P.G.); and Department of Brain Repair and Rehabilitation, Institute for Neurology, Queen Square, London, United..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariya","family":"Hristova","sequence":"additional","affiliation":[{"name":"From the Institute for Women\u2019s Health, University College London, London, United Kingdom (D.A.-A., K.D.B., M.C., S.D.F., A.K., J.H., E.R.-F., M.H., K.B., D.K., N.J.R.); Medical Physics and Bio-engineering, University College London Hospitals NHS Foundation Trust, London, United Kingdom (A.B., E.C.); Centre for the Developing Brain, King\u2019s College London, London, United Kingdom (B.F., P.G.); and Department of Brain Repair and Rehabilitation, Institute for Neurology, Queen Square, London, United..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bobbi","family":"Fleiss","sequence":"additional","affiliation":[{"name":"From the Institute for Women\u2019s Health, University College London, London, United Kingdom (D.A.-A., K.D.B., M.C., S.D.F., A.K., J.H., E.R.-F., M.H., K.B., D.K., N.J.R.); Medical Physics and Bio-engineering, University College London Hospitals NHS Foundation Trust, London, United Kingdom (A.B., E.C.); Centre for the Developing Brain, King\u2019s College London, London, United Kingdom (B.F., P.G.); and Department of Brain Repair and Rehabilitation, Institute for Neurology, Queen Square, London, United..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate","family":"Bennett","sequence":"additional","affiliation":[{"name":"From the Institute for Women\u2019s Health, University College London, London, United Kingdom (D.A.-A., K.D.B., M.C., S.D.F., A.K., J.H., E.R.-F., M.H., K.B., D.K., N.J.R.); Medical Physics and Bio-engineering, University College London Hospitals NHS Foundation Trust, London, United Kingdom (A.B., E.C.); Centre for the Developing Brain, King\u2019s College London, London, United Kingdom (B.F., P.G.); and Department of Brain Repair and Rehabilitation, Institute for Neurology, Queen Square, London, United..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorottya","family":"Kelen","sequence":"additional","affiliation":[{"name":"From the Institute for Women\u2019s Health, University College London, London, United Kingdom (D.A.-A., K.D.B., M.C., S.D.F., A.K., J.H., E.R.-F., M.H., K.B., D.K., N.J.R.); Medical Physics and Bio-engineering, University College London Hospitals NHS Foundation Trust, London, United Kingdom (A.B., E.C.); Centre for the Developing Brain, King\u2019s College London, London, United Kingdom (B.F., P.G.); and Department of Brain Repair and Rehabilitation, Institute for Neurology, Queen Square, London, United..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernest","family":"Cady","sequence":"additional","affiliation":[{"name":"From the Institute for Women\u2019s Health, University College London, London, United Kingdom (D.A.-A., K.D.B., M.C., S.D.F., A.K., J.H., E.R.-F., M.H., K.B., D.K., N.J.R.); Medical Physics and Bio-engineering, University College London Hospitals NHS Foundation Trust, London, United Kingdom (A.B., E.C.); Centre for the Developing Brain, King\u2019s College London, London, United Kingdom (B.F., P.G.); and Department of Brain Repair and Rehabilitation, Institute for Neurology, Queen Square, London, United..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Gressens","sequence":"additional","affiliation":[{"name":"From the Institute for Women\u2019s Health, University College London, London, United Kingdom (D.A.-A., K.D.B., M.C., S.D.F., A.K., J.H., E.R.-F., M.H., K.B., D.K., N.J.R.); Medical Physics and Bio-engineering, University College London Hospitals NHS Foundation Trust, London, United Kingdom (A.B., E.C.); Centre for the Developing Brain, King\u2019s College London, London, United Kingdom (B.F., P.G.); and Department of Brain Repair and Rehabilitation, Institute for Neurology, Queen Square, London, United..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Golay","sequence":"additional","affiliation":[{"name":"From the Institute for Women\u2019s Health, University College London, London, United Kingdom (D.A.-A., K.D.B., M.C., S.D.F., A.K., J.H., E.R.-F., M.H., K.B., D.K., N.J.R.); Medical Physics and Bio-engineering, University College London Hospitals NHS Foundation Trust, London, United Kingdom (A.B., E.C.); Centre for the Developing Brain, King\u2019s College London, London, United Kingdom (B.F., P.G.); and Department of Brain Repair and Rehabilitation, Institute for Neurology, Queen Square, London, United..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola J.","family":"Robertson","sequence":"additional","affiliation":[{"name":"From the Institute for Women\u2019s Health, University College London, London, United Kingdom (D.A.-A., K.D.B., M.C., S.D.F., A.K., J.H., E.R.-F., M.H., K.B., D.K., N.J.R.); Medical Physics and Bio-engineering, University College London Hospitals NHS Foundation Trust, London, United Kingdom (A.B., E.C.); Centre for the Developing Brain, King\u2019s College London, London, United Kingdom (B.F., P.G.); and Department of Brain Repair and Rehabilitation, Institute for Neurology, Queen Square, London, United..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.earlhumdev.2010.05.013"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0900854"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2005-0620E"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/pr.2012.8"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3174"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.CCM.0000069731.18472.61"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.WCB.0000066287.21705.21"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3468(80)80284-3"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1097\/PCC.0b013e3182975cc9"},{"key":"e_1_3_4_11_2","unstructured":"Shankaran S Laptook AR Pappas A McDonald SA Das A Tyson JE et al.. Effect of depth and duration of cooling on in-hospital mortality among neonates with hypoxic-ischemic encephalopathy: a randomized controlled trial. JAMA. In press."},{"key":"e_1_3_4_12_2","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1542\/peds.92.1.99","article-title":"Cerebral oxygen metabolism in newborns.","volume":"92","author":"Altman DI","year":"1993","unstructured":"Altman DI, Perlman JM, Volpe JJ, Powers WJ. Cerebral oxygen metabolism in newborns. Pediatrics. 1993;92:99\u2013104.","journal-title":"Pediatrics"},{"issue":"4","key":"e_1_3_4_13_2","first-page":"H869","article-title":"Hypothermia reduces cerebral metabolic rate and cerebral blood flow in newborn pigs.","volume":"253","author":"Busija DW","year":"1987","unstructured":"Busija DW, Leffler CW. Hypothermia reduces cerebral metabolic rate and cerebral blood flow in newborn pigs. Am J Physiol. 1987;253(4 pt 2):H869\u2013H873.","journal-title":"Am J Physiol"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1203\/01.PDR.0000072783.22373.FF"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.15-11-07250.1995"}],"container-title":["Stroke"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/STROKEAHA.114.007330","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,31]],"date-time":"2024-05-31T17:50:57Z","timestamp":1717177857000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/STROKEAHA.114.007330"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,1]]},"references-count":14,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2015,1]]}},"alternative-id":["10.1161\/STROKEAHA.114.007330"],"URL":"https:\/\/doi.org\/10.1161\/strokeaha.114.007330","relation":{},"ISSN":["0039-2499","1524-4628"],"issn-type":[{"value":"0039-2499","type":"print"},{"value":"1524-4628","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,1]]},"assertion":[{"value":"2014-09-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-10-28","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-11-25","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}