{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T03:46:34Z","timestamp":1760240794922,"version":"build-2065373602"},"reference-count":53,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2019,9,18]],"date-time":"2019-09-18T00:00:00Z","timestamp":1568764800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Cooperative Research Program for Agriculture Science and Technology Development","award":["Project No. PJ01329401"],"award-info":[{"award-number":["Project No. PJ01329401"]}]},{"name":"Rural Development Administration, Republic of Korea, and by the Bio &amp; Medical Technology Development Program of the NRF funded by the Korean government","award":["NRF-2015M3A9B6066968"],"award-info":[{"award-number":["NRF-2015M3A9B6066968"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Compelling evidence from preclinical and clinical studies has shown that mild hypothermia is neuroprotective against ischemic stroke. We investigated the neuroprotective effect of post-risperidone (RIS) treatment against transient ischemic injury and its mechanisms in the gerbil brain. Transient ischemia (TI) was induced in the telencephalon by bilateral common carotid artery occlusion (BCCAO) for 5 min under normothermic condition (37 \u00b1 0.2 \u00b0C). Treatment of RIS induced hypothermia until 12 h after TI in the TI-induced animals under uncontrolled body temperature (UBT) compared to that under controlled body temperature (CBT) (about 37 \u00b0C). Neuroprotective effect was statistically significant when we used 5 and 10 mg\/kg doses (p &lt; 0.05, respectively). In the RIS-treated TI group, many CA1 pyramidal neurons of the hippocampus survived under UBT compared to those under CBT. In this group under UBT, post-treatment with RIS to TI-induced animals markedly attenuated the activation of glial cells, an increase of oxidative stress markers [dihydroethidium, 8-hydroxy-2\u2032 -deoxyguanosine (8-OHdG), and 4-Hydroxynonenal (4-HNE)], and a decrease of superoxide dismutase 2 (SOD2) in their CA1 pyramidal neurons. Furthermore, RIS-induced hypothermia was significantly interrupted by NBOH-2C-CN hydrochloride (a selective 5-HT2A receptor agonist), but not bromocriptine mesylate (a D2 receptor agonist). Our findings indicate that RIS-induced hypothermia can effectively protect neuronal cell death from TI injury through attenuation of glial activation and maintenance of antioxidants, showing that 5-HT2A receptor is involved in RIS-induced hypothermia. Therefore, RIS could be introduced to reduce body temperature rapidly and might be applied to patients for hypothermic therapy following ischemic stroke.<\/jats:p>","DOI":"10.3390\/ijms20184621","type":"journal-article","created":{"date-parts":[[2019,9,18]],"date-time":"2019-09-18T11:01:15Z","timestamp":1568804475000},"page":"4621","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Risperidone Treatment after Transient Ischemia Induces Hypothermia and Provides Neuroprotection in the Gerbil Hippocampus by Decreasing Oxidative Stress"],"prefix":"10.3390","volume":"20","author":[{"given":"Go Eun","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Radiology, Kangwon National University Hospital, Chuncheon, Gangwon 24289, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyun-Jin","family":"Tae","sequence":"additional","affiliation":[{"name":"Bio-Safety Research Institute, College of Veterinary Medicine, Jeonbuk National University, Iksan, Jeollabuk 54596, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tae-Kyeong","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, Gangwon 24341, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young Eun","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, Gangwon 24341, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeong Hwi","family":"Cho","sequence":"additional","affiliation":[{"name":"Bio-Safety Research Institute, College of Veterinary Medicine, Jeonbuk National University, Iksan, Jeollabuk 54596, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dae Won","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, and Research Institute of Oral Sciences, College of Dentistry, Gangnung-Wonju National University, Gangneung, Gangwon 25457, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joon Ha","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Anatomy, College of Korean Medicine, Dongguk University, Gyeongju, Gyeongbuk 38066, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji Hyeon","family":"Ahn","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University, Chuncheon, Gangwon 24252, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sungwoo","family":"Ryoo","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, College of Natural Sciences, Kangwon National University, Chuncheon, Gangwon 24341, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8326-7768","authenticated-orcid":false,"given":"Young-Myeong","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chuncheon, Gangwon 24341, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Myoung Cheol","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, School of Medicine, Kangwon National University, Chuncheon, Gangwon 24341, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun Hwi","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, School of Medicine, Kangwon National University, Chuncheon, Gangwon 24341, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Choong-Hyun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, College of Pharmacy, Dankook University, Cheonan, Chungcheongnam 31116, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0533-4638","authenticated-orcid":false,"given":"In Koo","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, College of Veterinary Medicine, and Research Institute for Veterinary Science, Seoul National University, Seoul 08826, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Jin","sequence":"additional","affiliation":[{"name":"Center for Nutraceutical and Pharmaceutical Materials, Myongji University, Yongin, Gyeonggi 17058, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jae-Chul","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, Gangwon 24341, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,9,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1111\/j.1747-4949.2012.00770.x","article-title":"Neuroprotection for ischaemic stroke: Translation from the bench to the bedside","volume":"7","author":"Sutherland","year":"2012","journal-title":"Int. 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