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The HI injury causes mitochondrial damage leading to increased production of reactive oxygen species (ROS). Phytoestrogens are non\u2010steroidal plant substances structurally and functionally similar to estrogen. Coumestrol is a potent isoflavonoid with a protective effect against ischemic brain damage in adult rats. Our aim was to determine if coumestrol treatment following neonatal HI attenuates the long\u2010term cognitive deficits induced by neonatal HI, as well as to investigate one possible mechanism underlying its potential effect.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>On the 7th postnatal day, male Wistar rats were submitted to the Levine\u2010Rice HI model. Intraperitoneal injections of 20\u202fmg\/kg of coumestrol, or vehicle, were administered immediately pre\u2010hypoxia or 3\u202fh post\u2010hypoxia. At 12\u202fh after HI the mitochondrial status and ROS levels were determined. At 60th postnatal day the cognitive deficits were revealed in the Morris water maze reference and working spatial memories. Following behavioral analysis, histological assessment was performed and reactive astrogliosis was measured by GFAP expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Results demonstrate that both pre\u2010 and post\u2010HI administration of coumestrol were able to counteract the long\u2010term cognitive and morphological impairments caused by HI, as well as to block the late reactive astrogliosis. The pre\u2010HI administration of coumestrol was able to prevent the early mitochondrial dysfunction in the hippocampus of injured rat pups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Present data suggest that coumestrol exerts protection against experimental neonatal brain hypoxia\u2010ischemia through, at least in part, early modulation of mitochondrial function.<\/jats:p><\/jats:sec>","DOI":"10.1016\/j.ijdevneu.2019.10.009","type":"journal-article","created":{"date-parts":[[2019,11,3]],"date-time":"2019-11-03T18:35:49Z","timestamp":1572806149000},"page":"86-95","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Phytoestrogen coumestrol attenuates brain mitochondrial dysfunction and long\u2010term cognitive deficits following neonatal hypoxia\u2013ischemia"],"prefix":"10.1002","volume":"79","author":[{"given":"Janine Beatriz Ramos","family":"Anastacio","sequence":"first","affiliation":[{"name":"Post\u2010graduation Program in Biochemistry Universidade Federal do Rio Grande do Sul (UFRGS) Porto Alegre RS Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eduardo Farias","family":"Sanches","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Institute of Basic Health Sciences Universidade Federal do Rio Grande do Sul (UFRGS) Porto Alegre RS Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabr\u00edcio","family":"Nicola","sequence":"additional","affiliation":[{"name":"Post\u2010graduation Program in Neuroscience Universidade Federal do Rio Grande do Sul (UFRGS) Porto Alegre RS Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Felipe","family":"Odorcyk","sequence":"additional","affiliation":[{"name":"Post\u2010graduation Program in Phisiology Universidade Federal do Rio Grande do Sul (UFRGS) Porto Alegre RS Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rafael Bandeira","family":"Fabres","sequence":"additional","affiliation":[{"name":"Post\u2010graduation Program in Phisiology Universidade Federal do Rio Grande do Sul (UFRGS) Porto Alegre RS Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos Alexandre","family":"Netto","sequence":"additional","affiliation":[{"name":"Post\u2010graduation Program in Biochemistry Universidade Federal do Rio Grande do Sul (UFRGS) Porto Alegre RS Brazil"},{"name":"Department of Biochemistry Institute of Basic Health Sciences Universidade Federal do Rio Grande do Sul (UFRGS) Porto Alegre RS Brazil"},{"name":"Post\u2010graduation Program in Neuroscience Universidade Federal do Rio Grande do Sul (UFRGS) Porto Alegre RS Brazil"},{"name":"Post\u2010graduation Program in Phisiology Universidade Federal do Rio Grande do Sul (UFRGS) Porto Alegre RS Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,11,3]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10616\u2010008\u20109143\u20102"},{"key":"e_1_2_8_3_1","doi-asserted-by":"crossref","unstructured":"O.Arteaga A.\u00c1lvarez M.Revuelta F.Santaolalla A.Urtasun E.Hilario.Role of antioxidants in neonatal hypoxic\u2013ischemic brain injury: new therapeutic approaches.Int. 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