{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T00:09:26Z","timestamp":1777939766567,"version":"3.51.4"},"reference-count":55,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T00:00:00Z","timestamp":1709251200000},"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":[[2024,3,1]]},"abstract":"<jats:p>\n                    Therapeutic hypothermia (TH) mitigates damage in ischemic stroke models. However, safer and easier TH methods (e.g., pharmacological) are needed to circumvent physical cooling complications. This study evaluated systemic and pharmacologically induced TH using the adenosine A\n                    <jats:sub>1<\/jats:sub>\n                    receptor agonist, N\n                    <jats:sub>6<\/jats:sub>\n                    -cyclohexyladenosine (CHA), with control groups in male Sprague\u2013Dawley rats. CHA was administered intraperitoneally 10 minutes following a 2-hour intraluminal middle cerebral artery occlusion. We used a 1.5\u2009mg\/kg induction dose, followed by three 1.0\u2009mg\/kg doses every 6 hours for a total of 4 doses, causing 20\u201324 hours of hypothermia. Animals assigned to physical hypothermia and CHA-hypothermia had similar induction rates and nadir temperatures, but forced cooling lasted \u223c6 hours longer compared with CHA-treated animals. The divergence is likely attributable to individual differences in CHA metabolism, which led to varied durations at nadir, whereas physical hypothermia was better regulated. Physical hypothermia significantly reduced infarction (primary endpoint) on day 7 (mean reduction of 36.8\u2009mm\n                    <jats:sup>3<\/jats:sup>\n                    or 39% reduction;\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    \u2009=\u20090.021 vs. normothermic animals; Cohen's\n                    <jats:italic toggle=\"yes\">d<\/jats:italic>\n                    \u2009=\u20090.75), whereas CHA-induced hypothermia did not (\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    \u2009=\u20090.33). Similarly, physical cooling improved neurological function (physical hypothermia median\u2009=\u20090, physical normothermia median\u2009=\u20092;\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    \u2009=\u20090.008) and CHA-induced cooling did not (\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    \u2009&gt;\u20090.99). Our findings demonstrate that forced cooling was neuroprotective compared with controls, but prolonged CHA-induced cooling was not neuroprotective.\n                  <\/jats:p>","DOI":"10.1089\/ther.2023.0025","type":"journal-article","created":{"date-parts":[[2023,6,20]],"date-time":"2023-06-20T16:43:58Z","timestamp":1687279438000},"page":"36-45","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["An Assessment of Physical and N6-Cyclohexyladenosine-Induced Hypothermia in Rodent Distal Focal Ischemic Stroke"],"prefix":"10.1177","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9559-2592","authenticated-orcid":false,"given":"Lane J.","family":"Liddle","sequence":"first","affiliation":[{"name":"Department of Psychology, University of Alberta, Edmonton, Alberta, Canada."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi-Ge","family":"Huang","sequence":"additional","affiliation":[{"name":"Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiffany F.C.","family":"Kung","sequence":"additional","affiliation":[{"name":"Department of Psychology, University of Alberta, Edmonton, Alberta, Canada."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9753-6711","authenticated-orcid":false,"given":"Philipp","family":"Mergenthaler","sequence":"additional","affiliation":[{"name":"Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom."},{"name":"Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Center for Stroke Research Berlin, Berlin, Germany."},{"name":"Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Department of Neurology with Experimental Neurology, NeuroCure Clinical Research Center, Berlin, Germany."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frederick","family":"Colbourne","sequence":"additional","affiliation":[{"name":"Department of Psychology, University of Alberta, Edmonton, Alberta, Canada."},{"name":"Neuroscience and Mental Health Institute, University of Alberta, Edmonton, Alberta, Canada."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alastair M.","family":"Buchan","sequence":"additional","affiliation":[{"name":"Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom."},{"name":"Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Center for Stroke Research Berlin, Berlin, Germany."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2024,3,5]]},"reference":[{"key":"e_1_3_7_2_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2003.047928"},{"key":"e_1_3_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3475"},{"key":"e_1_3_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(18)30314-4"},{"key":"e_1_3_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.1992.86"},{"key":"e_1_3_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2008.04.016"},{"key":"e_1_3_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2009.10.002"},{"key":"e_1_3_7_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200102223440803"},{"key":"e_1_3_7_9_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.15-11-07250.1995"},{"key":"e_1_3_7_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004647-199907000-00003"},{"key":"e_1_3_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-0270(96)00047-7"},{"key":"e_1_3_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(89)90058-9"},{"key":"e_1_3_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1046-2023(03)00080-X"},{"key":"e_1_3_7_14_1","doi-asserted-by":"crossref","unstructured":"Dirnagl U. 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