{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T15:44:33Z","timestamp":1778600673685,"version":"3.51.4"},"reference-count":53,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,2,20]],"date-time":"2024-02-20T00:00:00Z","timestamp":1708387200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Korean Government (MSIP)","award":["2017R1C1B507687314"],"award-info":[{"award-number":["2017R1C1B507687314"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Therapeutic hypothermia (TH) shows promise as an approach with neuroprotective effects, capable of reducing secondary brain damage and intracranial pressure following successful mechanical thrombectomy in the acute phase. However, its effect on cognitive impairment remains unclear. This study investigated whether TH can improve cognitive impairment in a mouse model of transient middle cerebral artery occlusion followed by reperfusion (tMCAO\/R). Materials and Methods: Nine-week-old C57BL\/6N mice (male) were randomly assigned to three groups: sham, tMCAO\/R, and tMCAO\/R with TH. Cognitive function was assessed 1 month after model induction using the Y-maze test, and regional cerebral glucose metabolism was measured through positron emission tomography with fluorine-18 fluorodeoxyglucose. Results: tMCAO\/R induced cognitive impairment, which showed improvement with TH. The TH group exhibited a significant recovery in cerebral glucose metabolism in the thalamus compared to the tMCAO\/R group. Conclusions: These findings indicate that TH may hold promise as a therapeutic strategy for alleviating ischemia\/reperfusion-induced cognitive impairment.<\/jats:p>","DOI":"10.3390\/medicina60030350","type":"journal-article","created":{"date-parts":[[2024,2,20]],"date-time":"2024-02-20T04:04:14Z","timestamp":1708401854000},"page":"350","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Neuroprotective Effect of Therapeutic Hypothermia in Cognitive Impairment of an Ischemia\/Reperfusion Injury Mouse Model"],"prefix":"10.3390","volume":"60","author":[{"given":"Ji Sun","family":"Lim","sequence":"first","affiliation":[{"name":"Department of Nuclear Medicine, Keimyung University Dongsan Hospital, Daegu 42601, Republic of Korea"},{"name":"Department of Neurology, Keimyung University Dongsan Hospital, Daegu 42601, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1099-5027","authenticated-orcid":false,"given":"Shin","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Medicine, Keimyung University, Daegu 42601, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mee-Na","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Keimyung University Dongsan Hospital, Daegu 42601, Republic of Korea"},{"name":"Department of Neurology, Keimyung University Dongsan Hospital, Daegu 42601, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3631-3028","authenticated-orcid":false,"given":"Hyunsu","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Physiology, Pusan National University School of Medicine, Yangsan 50612, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hye Suk","family":"Baek","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Medicine, Keimyung University, Daegu 42601, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin Kyung","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Microbiology, School of Medicine, Keimyung University, Daegu 42601, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hae Won","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Keimyung University Dongsan Hospital, Daegu 42601, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8235-9855","authenticated-orcid":false,"given":"Jeong-Ho","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Neurology, Keimyung University Dongsan Hospital, Daegu 42601, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1080\/17434440.2020.1784004","article-title":"Recent advances in devices for mechanical thrombectomy","volume":"17","author":"Blanc","year":"2020","journal-title":"Expert Rev. Med. Devices"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1796","DOI":"10.1161\/STROKEAHA.117.017286","article-title":"Targeting reperfusion injury in the age of mechanical thrombectomy","volume":"49","author":"Mizuma","year":"2018","journal-title":"Stroke"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Higashi, Y., Aratake, T., Shimizu, T., Shimizu, S., and Saito, M. (2021). Protective role of glutathione in the hippocampus after brain ischemia. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22157765"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1038\/s41401-021-00650-3","article-title":"Exogenous glutathione exerts a therapeutic effect in ischemic stroke rats by interacting with intrastriatal dopamine","volume":"43","author":"Wang","year":"2022","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1169320","DOI":"10.3389\/fnmol.2023.1169320","article-title":"Neuron-astrocyte omnidirectional signaling in neurological health and disease","volume":"16","author":"Pathak","year":"2023","journal-title":"Front. Mol. Neurosci."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Iskusnykh, I.Y., Zakharova, A.A., and Pathak, D. (2022). Glutathione in brain disorders and aging. Molecules, 27.","DOI":"10.3390\/molecules27010324"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1038\/nature21029","article-title":"Neurotoxic reactive astrocytes are induced by activated microglia","volume":"541","author":"Liddelow","year":"2017","journal-title":"Nature"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/s42466-020-00079-9","article-title":"Bridging therapy is associated with improved cognitive function after large vessel occlusion stroke\u2014An analysis of the German Stroke Registry","volume":"2","author":"Ettelt","year":"2020","journal-title":"Neurol. Res. Pract."},{"key":"ref_9","first-page":"80","article-title":"Post-stroke cognitive impairment: Epidemiology, mechanisms and management","volume":"2","author":"Sun","year":"2014","journal-title":"Ann. Transl. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1161\/01.STR.32.2.413","article-title":"Stroke severity determines body temperature in acute stroke","volume":"32","author":"Boysen","year":"2001","journal-title":"Stroke"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1186\/s13054-016-1376-4","article-title":"The neurological and cognitive consequences of hyperthermia","volume":"20","author":"Walter","year":"2016","journal-title":"Crit. Care"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.1161\/STROKEAHA.119.028160","article-title":"Impact of body temperature before and after endovascular thrombectomy for large vessel occlusion stroke","volume":"51","author":"Diprose","year":"2020","journal-title":"Stroke"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1097\/00004647-200001000-00015","article-title":"Estrogen receptor antagonist ICI182, 780 exacerbates ischemic injury in female mouse","volume":"20","author":"Sawada","year":"2000","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_14","first-page":"9","article-title":"the effect of hypothermia on cognitive impairment and anxiety-like behavior in a cardiac arrest mouse model","volume":"42","author":"Lee","year":"2023","journal-title":"Quant. BioSci"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2171","DOI":"10.1161\/01.STR.29.10.2171","article-title":"Optimal depth and duration of mild hypothermia in a focal model of transient cerebral ischemia: Effects on neurologic outcome, infarct size, apoptosis, and inflammation","volume":"29","author":"Maier","year":"1998","journal-title":"Stroke"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.brainres.2016.05.042","article-title":"Hypothermia-induced ischemic tolerance is associated with Drp1 inhibition in cerebral ischemia-reperfusion injury of mice","volume":"1646","author":"Tang","year":"2016","journal-title":"Brain Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1939","DOI":"10.1161\/01.STR.31.8.1939","article-title":"Cognitive deficits after focal cerebral ischemia in mice","volume":"31","author":"Hattori","year":"2000","journal-title":"Stroke"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2875","DOI":"10.1161\/STROKEAHA.119.026652","article-title":"Validity and reliability of neurological scores in mice exposed to middle cerebral artery occlusion","volume":"50","author":"Bieber","year":"2019","journal-title":"Stroke"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1007\/s11655-017-2812-2","article-title":"Angelica tenuissima Nakai ameliorates cognitive impairment and promotes neurogenesis in mouse model of Alzheimer\u2019s disease","volume":"24","author":"Choi","year":"2018","journal-title":"Chin. J. Integr. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"14102","DOI":"10.1038\/s41598-019-50681-4","article-title":"The effect of chronic cerebral hypoperfusion on the pathology of Alzheimer\u2019s disease: A positron emission tomography study in rats","volume":"9","author":"Park","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Casteels, C., Vunckx, K., Aelvoet, S.-A., Baekelandt, V., Bormans, G., Van Laere, K., and Koole, M. (2013). Construction and evaluation of quantitative small-animal PET probabilistic atlases for [18F] FDG and [18F] FECT functional mapping of the mouse brain. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0065286"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1062650","DOI":"10.3389\/fphar.2022.1062650","article-title":"Differentiated HT22 cells as a novel model for screening of serotonin reuptake inhibitors","volume":"13","author":"Lim","year":"2023","journal-title":"Front. Pharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"154568","DOI":"10.1016\/j.phymed.2022.154568","article-title":"Salidroside intensifies mitochondrial function of CoCl-damaged HT22 cells by stimulating PI3K-AKT-MAPK signaling pathway","volume":"109","author":"Hou","year":"2023","journal-title":"Phytomedicine"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2825","DOI":"10.1161\/STROKEAHA.114.004285","article-title":"Amyloid burden, neuroinflammation, and links to cognitive decline after ischemic stroke","volume":"45","author":"Thiel","year":"2014","journal-title":"Stroke"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.1161\/CIRCRESAHA.122.319951","article-title":"Post-stroke cognitive impairment and dementia","volume":"130","author":"Rost","year":"2022","journal-title":"Circ. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1161\/CIRCRESAHA.116.308426","article-title":"Vascular cognitive impairment","volume":"120","author":"Dichgans","year":"2017","journal-title":"Circ. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"28","DOI":"10.3389\/fnmol.2020.00028","article-title":"Targeting oxidative stress and inflammation to prevent ischemia-reperfusion injury","volume":"13","author":"Wu","year":"2020","journal-title":"Front. Mol. Neurosci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1007\/s12975-018-0642-y","article-title":"Mitochondrial dysfunction in stroke: Implications of stem cell therapy","volume":"10","author":"Sarmah","year":"2018","journal-title":"Transl. Stroke Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.2174\/1570159X16666180302115544","article-title":"Cell death mechanisms in stroke and novel molecular and cellular treatment options","volume":"16","author":"Sekerdag","year":"2018","journal-title":"Curr. Neuropharmacol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1152\/physrev.00011.2017","article-title":"Neuronal cell death","volume":"98","author":"Fricker","year":"2018","journal-title":"Physiol. Rev."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1007\/s12975-020-00806-z","article-title":"Cell death pathways in ischemic stroke and targeted pharmacotherapy","volume":"11","author":"Datta","year":"2020","journal-title":"Transl. Stroke Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2244","DOI":"10.1161\/STROKEAHA.108.541128","article-title":"Update of the stroke therapy academic industry roundtable preclinical recommendations","volume":"40","author":"Fisher","year":"2009","journal-title":"Stroke"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1159\/000324621","article-title":"Temperature management in stroke\u2013an unsolved, but important topic","volume":"31","author":"Kollmar","year":"2011","journal-title":"Cerebrovasc. Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"80","DOI":"10.3389\/fneur.2011.00080","article-title":"Therapeutic hypothermia in stroke and traumatic brain injury","volume":"2","author":"Faridar","year":"2011","journal-title":"Front. Neurol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1152\/physiol.00025.2021","article-title":"Physiological impact of hypothermia: The good, the bad, and the ugly","volume":"37","author":"Tveita","year":"2022","journal-title":"Physiology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"S381","DOI":"10.4103\/2152-7806.183492","article-title":"Therapeutic hypothermia and ischemic stroke: A literature review","volume":"7","author":"Tahir","year":"2016","journal-title":"Surg. Neurol. Int."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/0006-8993(92)91428-H","article-title":"Immediate or delayed mild hypothermia prevents focal cerebral infarction","volume":"587","author":"Xue","year":"1992","journal-title":"Brain Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1720","DOI":"10.1161\/01.STR.0000129653.22241.d7","article-title":"Temperature-regulated model of focal ischemia in the mouse: A study with histopathological and behavioral outcomes","volume":"35","author":"Barber","year":"2004","journal-title":"Stroke"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"S72","DOI":"10.1161\/STROKEAHA.110.595371","article-title":"Therapeutic hypothermia for brain ischemia: Where have we come and where do we go?","volume":"41","author":"Yenari","year":"2010","journal-title":"Stroke"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1177\/0271678X211055959","article-title":"Selective therapeutic cooling: To maximize benefits and minimize side effects related to hypothermia","volume":"42","author":"Wu","year":"2022","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"6890","DOI":"10.1038\/s41467-022-34735-2","article-title":"Hypothermia evoked by stimulation of medial preoptic nucleus protects the brain in a mouse model of ischaemia","volume":"13","author":"Zhang","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1038\/s41583-019-0132-6","article-title":"Oxidative stress, dysfunctional glucose metabolism and Alzheimer disease","volume":"20","author":"Butterfield","year":"2019","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.arr.2016.02.003","article-title":"Brain fluorodeoxyglucose (FDG) PET in dementia","volume":"30","author":"Kato","year":"2016","journal-title":"Ageing Res. Rev."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1016\/S1474-4422(20)30231-3","article-title":"Brain insulin resistance in Alzheimer\u2019s disease and related disorders: Mechanisms and therapeutic approaches","volume":"19","author":"Kellar","year":"2020","journal-title":"Lancet Neurol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.jalz.2017.09.011","article-title":"Evidence for brain glucose dysregulation in Alzheimer\u2019s disease","volume":"14","author":"An","year":"2018","journal-title":"Alzheimers Dement."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1016\/S1474-4422(21)00060-0","article-title":"Strategic infarct locations for post-stroke cognitive impairment: A pooled analysis of individual patient data from 12 acute ischaemic stroke cohorts","volume":"20","author":"Weaver","year":"2021","journal-title":"Lancet Neurol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1177\/0271678X17728162","article-title":"Strategic infarct location for post-stroke cognitive impairment: A multivariate lesion-symptom mapping study","volume":"38","author":"Zhao","year":"2018","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/S0022-510X(99)00267-1","article-title":"Cognitive dysfunction following thalamic stroke: A study of 16 cases and review of the literature","volume":"172","author":"Karussis","year":"2000","journal-title":"J. Neurol. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3934\/Neuroscience.2022001","article-title":"Cognitive and linguistic dysfunction after thalamic stroke and recovery process: Possible mechanism","volume":"9","author":"Obayashi","year":"2022","journal-title":"AIMS Neurosci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1033729","DOI":"10.3389\/fnins.2022.1033729","article-title":"Isoflurane has no effect on cognitive or behavioral performance in a mouse model of early-stage Alzheimer\u2019s disease","volume":"16","author":"Borgstedt","year":"2022","journal-title":"Front. Neurosci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1354","DOI":"10.1016\/j.neuropharm.2011.08.011","article-title":"Isoflurane induces hippocampal cell injury and cognitive impairments in adult rats","volume":"61","author":"Lin","year":"2011","journal-title":"Neuropharmacology"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Pathak, D., and Sriram, K. (2023). Molecular mechanisms underlying neuroinflammation elicited by occupational injuries and toxicants. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24032272"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1002\/glia.23544","article-title":"Stroke target identification guided by astrocyte transcriptome analysis","volume":"67","author":"Rakers","year":"2019","journal-title":"Glia"}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/60\/3\/350\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:02:39Z","timestamp":1760104959000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/60\/3\/350"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,20]]},"references-count":53,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,3]]}},"alternative-id":["medicina60030350"],"URL":"https:\/\/doi.org\/10.3390\/medicina60030350","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,20]]}}}