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Neuroprotective Effects of Betulinic Acid Hydroxamate in Intraventricular Hemorrhage-Induced Brain Damage in Immature Rats
dc.contributor.author | Muñoz, Eduardo | |
dc.contributor.author | Martínez-Orgado, José | |
dc.contributor.author | Del Pozo, Aarón | |
dc.contributor.author | Silva, Laura | |
dc.contributor.author | Romero, Ángela | |
dc.contributor.author | De Hoz-Rivera, María | |
dc.contributor.author | Villa, María | |
dc.contributor.author | Martínez-Vega, María | |
dc.contributor.author | Prados, María E. | |
dc.contributor.author | Muñoz, Eduardo | |
dc.contributor.author | Martínez-Orgado, José | |
dc.date.accessioned | 2022-12-15T12:00:28Z | |
dc.date.available | 2022-12-15T12:00:28Z | |
dc.date.issued | 2022 | |
dc.identifier.uri | http://hdl.handle.net/10396/24397 | |
dc.description.abstract | 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 B55α/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-κB and TNFα 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. | es_ES |
dc.format.mimetype | application/pdf | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | MDPI | es_ES |
dc.rights | https://creativecommons.org/licenses/by/4.0/ | es_ES |
dc.source | Nutrients, 14(24), 5286 (2022) | es_ES |
dc.subject | Betulinic acid hydroxamate | es_ES |
dc.subject | Intraventricular hemorrhage | es_ES |
dc.subject | Neuroprotection | es_ES |
dc.subject | Prematurity | es_ES |
dc.subject | Rats | es_ES |
dc.title | Neuroprotective Effects of Betulinic Acid Hydroxamate in Intraventricular Hemorrhage-Induced Brain Damage in Immature Rats | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.relation.publisherversion | https://doi.org/10.3390/nu14245286 | es_ES |
dc.relation.projectID | Gobierno de España. PI19/00927 | es_ES |
dc.relation.projectID | Gobierno de España. RD21/0012/0023 | es_ES |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es_ES |