{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T07:42:04Z","timestamp":1782978124890,"version":"3.54.5"},"reference-count":69,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2024,12,1]],"date-time":"2024-12-01T00:00:00Z","timestamp":1733011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,12,1]],"date-time":"2024-12-01T00:00:00Z","timestamp":1733011200000},"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":["Therapeutic Hypothermia and Temperature Management"],"published-print":{"date-parts":[[2024,12,1]]},"abstract":"<jats:p>\n                    Therapeutic hypothermia (TH) lessens ischemic brain injury. Cytoprotective agents can augment protection, although it is unclear which combinations are most effective. The objective of this study is to identify which cytoprotective drug works best with delayed TH. Following PRISMA guidelines, a systematic review (PubMed, Web of Science, MEDLINE, Scopus) identified controlled experiments that used an\n                    <jats:italic toggle=\"yes\">in\u00a0vivo<\/jats:italic>\n                    focal ischemic stroke model and evaluated the efficacy of TH (delay of \u22651 hour) coupled with cytoprotective agents. This combination was our main intervention compared with single treatments with TH, drug, or no treatment. Endpoints were brain injury and neurological impairment. The CAMARADES checklist for study quality and the SYRCLE\u2019s risk of bias tool gauged study quality. Twenty-five studies were included. Most used young, healthy male rats, with only one using spontaneously hypertensive rats. Two studies used mice models, and six used adult animals. Study quality was moderate (median score = 6), and risk of bias was high. Pharmacological agents provided an additive effect on TH for all outcomes measured. Magnesium coupled with TH had the greatest impact compared with other agent-TH combinations on all outcomes. Longer TH durations improved both behavioral and histological outcomes and had greater cytoprotective efficacy than shorter durations. Anti-inflammatories were the most effective in reducing infarction (standardized mean difference [SMD]: \u22121.64, confidence interval [CI]: [\u22122.13, \u22121.15]), sulfonylureas reduced edema the most (SMD: \u22122.32, CI: [\u22123.09, \u22121.54]), and antiapoptotic agents improved behavioral outcomes the most (normalized mean difference: 52.38, CI: [45.29, 59.46]). Statistically significant heterogeneity was observed (\n                    <jats:italic toggle=\"yes\">I<\/jats:italic>\n                    <jats:sup>2<\/jats:sup>\n                    = 82\u2009\u2212\u200998%, all\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    &lt; 0.001), indicating that studies wildly differ in their effect size estimates. Our results support the superiority of adding cytoprotective therapies with TH (vs. individual or no therapy). Additional exploratory and confirmatory studies are required to identify and thoroughly assess combination therapies owing to limited work and inconsistent translational quality.\n                  <\/jats:p>","DOI":"10.1089\/ther.2024.0012","type":"journal-article","created":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T05:12:50Z","timestamp":1719810770000},"page":"229-242","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["A Systematic Review and Meta-Analysis of Therapeutic Hypothermia and Pharmacological Cotherapies in Animal Models of Ischemic Stroke"],"prefix":"10.1177","volume":"14","author":[{"given":"Angely Claire C.","family":"Suerte","sequence":"first","affiliation":[{"name":"Department of Psychology, Faculty of Science, University of Alberta, Edmonton, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9559-2592","authenticated-orcid":false,"given":"Lane J.","family":"Liddle","sequence":"additional","affiliation":[{"name":"Department of Psychology, Faculty of Science, University of Alberta, Edmonton, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley","family":"Abrahart","sequence":"additional","affiliation":[{"name":"Department of Psychology, Faculty of Science, University of Alberta, Edmonton, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elmira","family":"Khiabani","sequence":"additional","affiliation":[{"name":"Department of Psychology, Faculty of Science, University of Alberta, Edmonton, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9567-2082","authenticated-orcid":false,"given":"Frederick","family":"Colbourne","sequence":"additional","affiliation":[{"name":"Department of Psychology, Faculty of Science, University of Alberta, Edmonton, Canada."},{"name":"Neuroscience and Mental Health Institute, University of Alberta, Edmonton, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2024,12,16]]},"reference":[{"key":"e_1_3_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clineuro.2012.06.001"},{"key":"e_1_3_7_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/archdischild-2019-317311"},{"key":"e_1_3_7_4_1","doi-asserted-by":"publisher","DOI":"10.51847\/pMfN3Q005M"},{"key":"e_1_3_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-06752-5"},{"key":"e_1_3_7_6_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000068170.80517.B3"},{"key":"e_1_3_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2010.07.015"},{"key":"e_1_3_7_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm13020586"},{"key":"e_1_3_7_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-016-9695-7"},{"key":"e_1_3_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2016.01.010"},{"key":"e_1_3_7_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.23740"},{"key":"e_1_3_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2013.01.038"},{"key":"e_1_3_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2008.06.110"},{"key":"e_1_3_7_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/tropej\/fmaa073"},{"key":"e_1_3_7_15_1","doi-asserted-by":"publisher","DOI":"10.1089\/ther.2015.0010"},{"key":"e_1_3_7_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph182211817"},{"key":"e_1_3_7_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11011-021-00731-6"},{"key":"e_1_3_7_18_1","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X16645112"},{"key":"e_1_3_7_19_1","first-page":"0042","article-title":"Longer periods of hypothermia provide greater protection against focal ischemia: A systematic review of animal studies manipulating treatment duration","author":"Eberle MJ","year":"2023","unstructured":"Eberle MJ, , Thorkelsson AB, , Liddle LJ, et al. 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