{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:31:56Z","timestamp":1787027516029,"version":"build-2736575974"},"reference-count":50,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,9,16]],"date-time":"2024-09-16T00:00:00Z","timestamp":1726444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003451","name":"University of the Basque Country","doi-asserted-by":"publisher","award":["GIU21\/054"],"award-info":[{"award-number":["GIU21\/054"]}],"id":[{"id":"10.13039\/501100003451","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003451","name":"University of the Basque Country","doi-asserted-by":"publisher","award":["PIFINVE22\/14"],"award-info":[{"award-number":["PIFINVE22\/14"]}],"id":[{"id":"10.13039\/501100003451","id-type":"DOI","asserted-by":"publisher"}]},{"name":"EU-Next Generation","award":["GIU21\/054"],"award-info":[{"award-number":["GIU21\/054"]}]},{"name":"EU-Next Generation","award":["PIFINVE22\/14"],"award-info":[{"award-number":["PIFINVE22\/14"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Neonatal hypoxia\u2013ischemia is a major cause of infant death and disability. The only clinically accepted treatment is therapeutic hypothermia; however, cooling is less effective in the most severely encephalopathic infants. Here, we wanted to test the neuroprotective effect of the antioxidant dimethyl fumarate after severe hypoxia\u2013ischemia in neonatal rats. We used a modified Rice\u2013Vannucci model to generate severe hypoxic\u2013ischemic brain damage in day 7 postnatal rats, which were randomized into four experimental groups: Sham, Sham + DMF, non-treated HI, and HI + DMF. We analyzed brain tissue loss, global and regional (cortex and hippocampus) neuropathological scores, white matter injury, and microglial and astroglial reactivity. Compared to non-treated HI animals, HI + DMF pups showed a reduced brain area loss (p = 0.0031), an improved neuropathological score (p = 0.0016), reduced white matter injuries by preserving myelin tracts (p &lt; 0.001), and diminished astroglial (p &lt; 0.001) and microglial (p &lt; 0.01) activation. After severe hypoxia\u2013ischemia in neonatal rats, DMF induced a strong neuroprotective response, reducing cerebral infarction, gray and white matter damage, and astroglial and microglial activation. Although further molecular studies are needed and its translation to human babies would need to evaluate the molecule in piglets or lambs, DMF may be a potential treatment against neonatal encephalopathy.<\/jats:p>","DOI":"10.3390\/antiox13091122","type":"journal-article","created":{"date-parts":[[2024,9,16]],"date-time":"2024-09-16T10:56:57Z","timestamp":1726484217000},"page":"1122","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Dimethyl Fumarate Strongly Ameliorates Gray and White Matter Brain Injury and Modulates Glial Activation after Severe Hypoxia\u2013Ischemia in Neonatal Rats"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-8417-1563","authenticated-orcid":false,"given":"Jon Ander","family":"Alart","sequence":"first","affiliation":[{"name":"Department of Cell Biology and Histology, School of Medicine and Nursing, University of the Basque Country (UPV\/EHU), 48940 Leioa, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonia","family":"\u00c1lvarez","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Histology, School of Medicine and Nursing, University of the Basque Country (UPV\/EHU), 48940 Leioa, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0418-7904","authenticated-orcid":false,"given":"Ana","family":"Catalan","sequence":"additional","affiliation":[{"name":"Psychiatry Department, OSI Bilbao-Basurto, Basurto University Hospital, 48013 Bilbao, Spain"},{"name":"Neuroscience Department, University of the Basque Country (UPV\/EHU), 48013 Leioa, Spain"},{"name":"Biobizkaia Health Research Institute, 48903 Barakaldo, Spain"},{"name":"CIBERSAM, Centro Investigaci\u00f3n Biom\u00e9dica en Red de Salud Mental, 28007 Madrid, Spain"},{"name":"Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King\u2019s College London, London SE5 8AF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5988-1795","authenticated-orcid":false,"given":"Borja","family":"Herrero de la Parte","sequence":"additional","affiliation":[{"name":"Department of Surgery and Radiology and Physical Medicine, School of Medicine and Nursing, University of the Basque Country (UPV\/EHU), 48940 Leioa, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Alonso-Alconada","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Histology, School of Medicine and Nursing, University of the Basque Country (UPV\/EHU), 48940 Leioa, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1056\/NEJMoa2119660","article-title":"Trial of Erythropoietin for Hypoxic\u2013Ischemic Encephalopathy in Newborns","volume":"387","author":"Wu","year":"2022","journal-title":"N. 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