RT Journal Article
T1 Neuroprotective effects of betulinic acid hydroxamate in intraventricular hemorrhage-induced brain damage in immature rats
A1 del Pozo, A
A1 Silva, L
A1 Romero A, 
A1 de Hoz Riviera, M
A1 Villa, M
A1 Martinez Vega, M
A1 Prados, M. E.
A1 Muñoz, E
A1 Martínez Orgado, José Antonio
AB 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.
PB MDPI
YR 2022
FD 2022-12-12
LK https://hdl.handle.net/20.500.14352/118554
UL https://hdl.handle.net/20.500.14352/118554
LA eng
NO 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
NO Insitituto de Salud Carlos III
DS Docta Complutense
RD 11 abr 2025