{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T02:51:26Z","timestamp":1791687086860,"version":"4.3.4"},"reference-count":56,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,1,26]],"date-time":"2023-01-26T00:00:00Z","timestamp":1674691200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2020R1I1A3068251"],"award-info":[{"award-number":["NRF-2020R1I1A3068251"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF- 2021R1A2C1094224"],"award-info":[{"award-number":["NRF- 2021R1A2C1094224"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2022R1F1A1065996"],"award-info":[{"award-number":["NRF-2022R1F1A1065996"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Cardiac arrest (CA) and return of spontaneous circulation (ROSC), a global ischemia and reperfusion event, lead to neuronal damage and\/or death in the spinal cord as well as the brain. Hypothermic therapy is reported to protect neurons from damage and improve hindlimb paralysis after resuscitation in a rat model of CA induced by asphyxia. In this study, we investigated roles of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in the lumbar spinal cord protected by therapeutic hypothermia in a rat model of asphyxial CA. Male Sprague-Dawley rats were subjected to seven minutes of asphyxial CA (induced by injection of 2 mg\/kg vecuronium bromide) and hypothermia (four hours of cooling, 33 \u00b1 0.5 \u00b0C). Survival rate, hindlimb motor function, histopathology, western blotting, and immunohistochemistry were examined at 12, 24, and 48 h after CA\/ROSC. The rats of the CA\/ROSC and hypothermia-treated groups had an increased survival rate and showed an attenuated hindlimb paralysis and a mild damage\/death of motor neurons located in the anterior horn of the lumbar spinal cord compared with those of the CA\/ROSC and normothermia-treated groups. In the CA\/ROSC and hypothermia-treated groups, expressions of cytoplasmic and nuclear Nrf2 and HO-1 were significantly higher in the anterior horn compared with those of the CA\/ROSC and normothermia-treated groups, showing that cytoplasmic and nuclear Nrf2 was expressed in both motor neurons and astrocytes. Moreover, in the CA\/ROSC and hypothermia-treated group, interleukin-1\u03b2 (IL-1\u03b2, a pro-inflammatory cytokine) expressed in the motor neurons was significantly reduced, and astrocyte damage was apparently attenuated compared with those found in the CA\/ROSC and normothermia group. Taken together, our results indicate that hypothermic therapy after CA\/ROSC attenuates CA-induced hindlimb paralysis by protecting motor neurons in the lumbar spinal cord via activating the Nrf2\/HO-1 signaling pathway and attenuating pro-inflammation and astrocyte damage (reactive astrogliosis).<\/jats:p>","DOI":"10.3390\/cells12030414","type":"journal-article","created":{"date-parts":[[2023,1,27]],"date-time":"2023-01-27T02:30:38Z","timestamp":1674786638000},"page":"414","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Therapeutic Hypothermia after Cardiac Arrest Attenuates Hindlimb Paralysis and Damage of Spinal Motor Neurons and Astrocytes through Modulating Nrf2\/HO-1 Signaling Pathway in Rats"],"prefix":"10.3390","volume":"12","author":[{"given":"Ji Hyeon","family":"Ahn","sequence":"first","affiliation":[{"name":"Department of Physical Therapy, College of Health Science, Youngsan University, Yangsan, Gyeongnam 50510, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae-Kyeong","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University, Chuncheon, Gangwon 24252, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8785-4508","authenticated-orcid":false,"given":"Dae Won","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Research Institute of Oral Sciences, College of Dentistry, Kangnung-Wonju National University, Gangneung, Gangwon 25457, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myoung Cheol","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, School of Medicine, Kangwon National University, Chuncheon, Gangwon 24289, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun Hwi","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, School of Medicine, Kangwon National University, Chuncheon, Gangwon 24289, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae-Chul","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5193-508X","authenticated-orcid":false,"given":"Hyun-Jin","family":"Tae","sequence":"additional","affiliation":[{"name":"Bio-Safety Research Institute, College of Veterinary Medicine, Chonbuk National University, Iksan, Chonbuk 54596, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joon Ha","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Anatomy, College of Korean Medicine, Dongguk University, Gyeongju, Gyeongbuk 38066, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seongkweon","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Surgery, Kangwon National University Hospital, School of Medicine, Kangwon National University, Chuncheon, Gangwon 24289, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5508-9004","authenticated-orcid":false,"given":"Choong-Hyun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, College of Pharmacy, Dankook University, Cheonan, Chungnam 31116, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7178-6501","authenticated-orcid":false,"given":"Moo-Ho","family":"Won","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2754-6412","authenticated-orcid":false,"given":"Yang Hee","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Surgery, Kangwon National University Hospital, School of Medicine, Kangwon National University, Chuncheon, Gangwon 24289, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2091","DOI":"10.1002\/ar.23694","article-title":"Arterial blood supply to the spinal cord in animal models of spinal cord injury. 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