RT Journal Article
T1 Neuroprotective effects of VCE-004.8 in a rat model of neonatal stroke
A1 Villa, María
A1 Martínez Vega, María
A1 Silva, Laura
A1 Romero, Ángela
A1 De Hoz Rivera, María
A1 Prados, María Eugenia
A1 Muñoz, Eduardo
A1 Martínez Orgado, José Antonio
AB BackgroundCurrently there is no effective treatment for neonatal stroke, an acute neurologic syndrome with sequelae, due to focal ischemic, thrombotic, or hemorrhagic event occurring in the perinatal period. VCE-004.8, an aminoquinone exhibiting activity on CB2 and PPARγ receptors, is neuroprotective in adult mice models of acute and chronic brain damaging conditions. We hereby aimed to study VCE-004.8 neuroprotection in a rat model of neonatal stroke.Methods7-day-old (P7) Wistar rats of both sexes were submitted to Middle Cerebral Artery Occlusion (MCAO), receiving i.p. 30 min after vehicle (MCAO + VEH) or VCE-004.8 5 mg/kg (MCAO + VCE). Non-occluded rats served as controls (SHAM). MCAO consequences were assessed at P14 by MRI, histological (TUNEL staining), biochemical (lactate/n-acetyl aspartate ratio by 1H-NMR spectroscopy) and motor studies (grasp test), and at P37 assessing myelination (MBP signal), hemiparesis and hyperlocomotion. Effects of VCE-004.8 on excitotoxicity (glutamate/n-acetyl aspartate, 1H-NMR), oxidative stress (protein nitrosylation, Oxyblot) and neuroinflammation (Toll-like receptor 4 and TNFa expression, Western blot) were assessed at P14. Therapeutic window was assessed by delaying drug administration for 12 or 18 h.ResultsPost-MCAO administration of VCE-004.8 reduced the volume of infarct and histological and biochemical brain damage, reducing hyperlocomotion, restoring motor performance and preserving myelination, in a manner linked to the modulation of excitotoxicity, oxidative stress and neuroinflammation. VCE-004.8 was still effective being administered 12–18 h post-insult.ConclusionsThese data suggest that this drug could be effective for the treatment of stroke in newborns.
PB Elsevier
SN 0014-2999
YR 2024
FD 2024-03-22
LK https://hdl.handle.net/20.500.14352/118549
UL https://hdl.handle.net/20.500.14352/118549
LA eng
NO Villa M, Martínez-Vega M, Silva L, Romero A, de Hoz-Rivera M, Prados ME, Muñoz E, Martínez-Orgado J. Neuroprotective effects of VCE-004.8 in a rat model of neonatal stroke. Eur J Pharmacol. 2024 Jun 5;972:176554. doi: 10.1016/j.ejphar.2024.176554
NO Fondos FEDER
NO European Commission
NO Instituto de Salud Carlos III (España)
DS Docta Complutense
RD 22 abr 2025