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oai:docta.ucm.es:20.500.14352/1185542025-08-29T15:08:45Zcom_20.500.14352_14col_20.500.14352_15

Neuroprotective effects of betulinic acid hydroxamate in intraventricular hemorrhage-induced brain damage in immature rats del Pozo, A Silva, L Romero A de Hoz Riviera , M Villa, M Martinez Vega, M Prados, M. E. Muñoz, E Martínez Orgado, José Antonio 616.831 Betulinic acid hydroxamate Intraventricular hemorrhage Neuroprotection Prematurity Rats Neurociencias (Medicina) 3205.07 Neurología 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. Instituto de Salud Carlos III Depto. de Salud Pública y Materno - Infantil Fac. de Medicina TRUE pub 2025-03-06T08:59:11Z 2025-03-06T08:59:11Z 2022-12-12 journal article VoR https://hdl.handle.net/20.500.14352/118554 XXXX-XXXX 10.3390/nu14245286. eng info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII)/PI19%2F00927/ES/LA UNIDAD NEUROVASCULAR COMO DIANA TERAPEUTICA PARA PREVENIR LAS SECUELAS DEL INFARTO ARTERIAL CEREBRAL ISQUEMICO NEONATAL EN UN MODELO EN RATA/ info:eu-repo/grantAgreement/ISCIII/RD21/0012/0023 Del Pozo, A., Silva, L., Romero, A., De Hoz-Rivera, M., Villa, M., Martínez-Vega, M., Prados, M. E., Muñoz, E., & Martínez-Orgado, J. (2022). Neuroprotective Effects of Betulinic Acid Hydroxamate in Intraventricular Hemorrhage-Induced Brain Damage in Immature Rats. Nutrients, 14(24), 5286. https://doi.org/10.3390/nu14245286 Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ open access application/pdf MDPI