{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T12:00:29Z","timestamp":1790164829944,"version":"4.1.0"},"reference-count":32,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2016,9,9]],"date-time":"2016-09-09T00:00:00Z","timestamp":1473379200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Dr Ramana-Kumar Agnihotram"},{"name":"Pr Claire Dubois for the editing of the manuscript and the mentorship"},{"name":"Armin Yazdani and Noha Gerges for the english revisions"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl J of Devlp Neuroscience"],"published-print":{"date-parts":[[2016,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Despite the recent introduction of hypothermia as a mandatory standard of care, the incidence of neonatal encephalopathy in full\u2010term newborns and its devastating neuro\u2010behavioral outcomes continues to be a major individual, familial and social issue. Neonatal encephalopathy is mainly due to the compounding and interacting effects of hypoxia\u2010ischemia and inflammation resulting from placental and other perinatal infections. It is unclear why hypothermia is effective in alleviating neonatal encephalopathy in some, but not all, full\u2010term newborns. However, newborns exposed to inflammatory\u2010sensitized hypoxia\u2010ischemia seem to have less therapeutic benefit from hypothermia than those exposed to hypoxia\u2010ischemia alone.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To clarify this uncertainty, we tested the efficacy of hypothermia in a double\u2010hit model of neonatal encephalopathy induced by inflammatory\u2010sensitized hypoxia\u2010ischemia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using a rat preclinical model of endotoxin plus hypoxia\u2010ischemia\u2010induced neonatal encephalopathy of term newborns, we assessed the following in pups exposed (or not) to hypothermia: the extent of brain injuries and the expressions of molecules implicated in neural cell death, namely: pro\u2010inflammatory cytokines, matrix metalloproteinase\u20109, antioxidant enzymes, as well as receptor\u2010interacting protein\u20103.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Hypothermia was neuroprotective on inflammatory\u2010sensitized hypoxia\u2010ischemia\u2010induced penumbra, but not core, brain injuries. This beneficial effect was associated with a hypothermia\u2010induced increase of antioxidant enzymes (superoxide dismutase\u20101, glutathione peroxidase\u20101), but was not associated with any variations of the other inflammatory mediators tested, namely: interleukin\u20101\u03b2, interleukin\u20101 receptor antagonist, tumor necrosis factor\u2010\u03b1 and matrix metalloproteinase\u20109.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Hypothermia is neuroprotective against inflammatory\u2010sensitized hypoxia\u2010ischemia possibly through a hypothermia\u2010induced increase of antioxidant enzymes. This neuroprotective effect seems to be independent of the interleukin\u20101 system.<\/jats:p><\/jats:sec>","DOI":"10.1016\/j.ijdevneu.2016.09.002","type":"journal-article","created":{"date-parts":[[2016,9,12]],"date-time":"2016-09-12T21:30:55Z","timestamp":1473715855000},"page":"1-8","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Neuroprotective effects of hypothermia in inflammatory\u2010sensitized hypoxic\u2010ischemic encephalopathy"],"prefix":"10.1002","volume":"55","author":[{"given":"Mathilde","family":"Chevin","sequence":"first","affiliation":[{"name":"D\u00e9partement de P\u00e9diatrie Universit\u00e9 de Sherbrooke 3001\u2010 12e avenue Nord Sherbrooke Quebec J1H 5N4 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cl\u00e9mence","family":"Guiraut","sequence":"additional","affiliation":[{"name":"Department of Pediatrics McGill University, Research Institute of the McGill 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