{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T01:55:44Z","timestamp":1790906144411,"version":"4.1.0"},"reference-count":33,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2022,12,12]],"date-time":"2022-12-12T00:00:00Z","timestamp":1670803200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"PI19\/00927 and RD21\/0012\/0023 projects"},{"name":"ISCIII"},{"name":"European Regional Development Fund (ERDF)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Intraventricular hemorrhage (IVH) is an important cause of long-term disability in extremely preterm infants, with no current treatment. We aimed to study in an IVH model in immature rats the neuroprotective effect of betulinic acid hydroxamate (BAH), a B55\u03b1\/PP2A activator that inhibits the activity of the hypoxia-inducing factor prolyl-hydroxylase type 2. IVH was induced in 1-day-old (P1) Wistar rats by the left periventricular injection of Clostridial collagenase. Then, pups received i.p. vehicle or BAH 3 mg\/kg single dose. At P6, P14 and P45, brain damage (area of damage, neurobehavioral deficits, Lactate\/N-acetylaspartate ratio), white matter injury (WMI: corpus callosum atrophy and myelin basic protein signal reduction) and inflammation (TLR4, NF-\u03baB and TNF\u03b1 expression), excitotoxicity (Glutamate\/N-acetylspartate) and oxidative stress (protein nitrosylation) were evaluated. BAH treatment did not reduce the volume of brain damage, but it did reduce perilesional tissue damage, preventing an IVH-induced increase in Lac\/NAA. BAH restored neurobehavioral performance at P45 preventing WMI. BAH prevented an IVH-induced increase in inflammation, excitotoxicity and oxidative stress. In conclusion, in immature rats, BAH reduced IVH-induced brain damage and prevented its long-term functional consequences, preserving normal myelination in a manner related to the modulation of inflammation, excitotoxicity and oxidative stress.<\/jats:p>","DOI":"10.3390\/nu14245286","type":"journal-article","created":{"date-parts":[[2022,12,12]],"date-time":"2022-12-12T04:05:22Z","timestamp":1670817922000},"page":"5286","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Neuroprotective Effects of Betulinic Acid Hydroxamate in Intraventricular Hemorrhage-Induced Brain Damage in Immature Rats"],"prefix":"10.3390","volume":"14","author":[{"given":"Aar\u00f3n","family":"Del Pozo","sequence":"first","affiliation":[{"name":"Biomedical Research Foundation, Hospital Cl\u00ednico San Carlos\u2014IdISSC, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Silva","sequence":"additional","affiliation":[{"name":"Biomedical Research Foundation, Hospital Cl\u00ednico San Carlos\u2014IdISSC, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Romero","sequence":"additional","affiliation":[{"name":"Biomedical Research Foundation, Hospital Cl\u00ednico San Carlos\u2014IdISSC, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"De Hoz-Rivera","sequence":"additional","affiliation":[{"name":"Biomedical Research Foundation, Hospital Cl\u00ednico San Carlos\u2014IdISSC, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9394-4323","authenticated-orcid":false,"given":"Mar\u00eda","family":"Villa","sequence":"additional","affiliation":[{"name":"Biomedical Research Foundation, Hospital Cl\u00ednico San Carlos\u2014IdISSC, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Mart\u00ednez-Vega","sequence":"additional","affiliation":[{"name":"Biomedical Research Foundation, Hospital Cl\u00ednico San Carlos\u2014IdISSC, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Eugenia","family":"Prados","sequence":"additional","affiliation":[{"name":"Vivacell Biotechnology Espa\u00f1a S.L.U., 14014 C\u00f3rdoba, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8478-5842","authenticated-orcid":false,"given":"Eduardo","family":"Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"Maimonides Biomedical Research Institute of C\u00f3rdoba, University of C\u00f3rdoba, 14004 C\u00f3rdoba, Spain"},{"name":"Department of Cellular Biology, Physiology and Immunology, University of C\u00f3rdoba, 14004 C\u00f3rdoba, Spain"},{"name":"Reina Sof\u00eda University Hospital, 14004 C\u00f3rdoba, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4405-3545","authenticated-orcid":false,"given":"Jos\u00e9","family":"Mart\u00ednez-Orgado","sequence":"additional","affiliation":[{"name":"Biomedical Research Foundation, Hospital Cl\u00ednico San Carlos\u2014IdISSC, 28040 Madrid, Spain"},{"name":"Department of Neonatology, Hospital Cl\u00ednico San Carlos\u2014IdISSC, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.clp.2013.09.007","article-title":"Pathogenesis and Prevention of Intraventricular Hemorrhage","volume":"41","author":"Ballabh","year":"2014","journal-title":"Clin. 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