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Hypothermia plays a beneficial role in central nervous system diseases. However, the role of hypothermia in IS has not yet been elucidated. In this study, we determined the role of hypothermia in IS and explored its underlying mechanisms. The IS phenotype was detected based on infarct size, infarct volume, and brain edema in mice. Neuroinflammation was evaluated by the activation of microglial cells and the expression of inflammatory genes after ischemia\/reperfusion (I\/R) and oxygen\u2010glucose deprivation\/reperfusion (OGD\/R). Neuronal cell apoptosis, cleaved caspase\u20103 and Bax\/Bcl\u20102 expressions, cell viability, and lactate dehydrogenase (LDH) release were detected after I\/R and OGD\/R. Blood\u2013brain barrier (BBB) permeability was calculated based on Evans blue extravasation, tight junction protein expression, cell viability, and LDH release after I\/R and OGD\/R. The expression of peroxisome proliferator\u2010activated receptor gamma (PPAR<jats:italic>\u03b3<\/jats:italic>) was assessed after OGD\/R. Our results suggested that hypothermia significantly reduced infarct size, brain edema, and neuroinflammation after I\/R. Hypothermia increased PPAR<jats:italic>\u03b3<\/jats:italic> expression in microglial cells after OGD\/R. Mechanistic studies revealed that hypothermia was a protectant against IS, including attenuated apoptosis of neuronal cells and BBB disruption after I\/R and OGD\/R, by upregulating PPAR<jats:italic>\u03b3<\/jats:italic> expression. The hypothermic effect was reversed by GW9662, a PPAR<jats:italic>\u03b3<\/jats:italic> inhibitor. Our data showed that hypothermia may reduce microglial cell\u2010mediated neuroinflammation by upregulating PPAR<jats:italic>\u03b3<\/jats:italic> expression in microglial cells. Targeting hypothermia may be a feasible approach for IS treatment.<\/jats:p>","DOI":"10.1155\/2022\/6029445","type":"journal-article","created":{"date-parts":[[2022,7,14]],"date-time":"2022-07-14T21:20:15Z","timestamp":1657833615000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Hypothermia Protects against Ischemic Stroke through Peroxisome\u2010Proliferator\u2010Activated\u2010Receptor 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