Martínez Orgado, José AntonioFernádez Frutos, BeatrizGonzález, RitaRomero, EvaUrigüen, LeireRomero, JuliánViveros Hernando, María Paz2025-01-302025-01-302003-06-10Martínez-Orgado, J., Fernández-Frutos, B., González, R., Romero, E., Urigüen, L., Romero, J., & Viveros, M. P. (2003). Neuroprotection by the cannabinoid agonist WIN-55212 in an in vivo newborn rat model of acute severe asphyxia. Brain research. Molecular brain research, 114(2), 132–139. https://doi.org/10.1016/s0169-328x(03)00163-30169-328X10.1016/s0169-328x(03)00163-3.https://hdl.handle.net/20.500.14352/117072This study was designed to evaluate the neuroprotective effect of the cannabinoid agonist WIN-55212 after inducing acute severe asphyxia in newborn rats. The left common carotid artery was ligated in anaesthetised 7-day-old Wistar rats, which were then asphyxiated by inhaling 100% nitrogen for 10 min. Pups recovering from asphyxia were s.c. administered vehicle (n=23), WIN-55212 (0.1 mg/kg, n=18), or WIN-55212 plus the CB1 receptor antagonist SR141716 (3 mg/kg, n=10). Pups undergoing a sham operation served as controls (n=12). Coronal sections of the brain were obtained on the 14th day after surgery and observed under light microscope after Nissl or Fluoro-Jade B (FJB) staining, to respectively quantify surviving or degenerating neurones in the CA1 area of the hippocampus and parietal cortex. Acute asphyxia led to early neurone loss amounting to 19% in the hippocampus and 29% in the cortex (both ANOVA P<0.05 vs. control). Delayed neurone loss occurred in the proportions 13% in the hippocampus and 20% in the cortex (both ANOVA P<0.05 vs. control). Neuronal loss was fully prevented by WIN-55212 administration. Co-administration of SR141716 failed to modify the protective effect of WIN-55212 on early neuronal death, but abolished the WIN-55212-induced prevention of delayed neuronal death. We conclude that when administered after acute severe asphyxia in newborn rats, WIN-55212 shows a neuroprotective effect, reducing both early and delayed neurone loss. This effect is achieved through two parallel CB1-dependent and -independent mechanisms.engjournal articlehttps://doi.org/10.1016/S0169-328X(03)00163-3https://www.sciencedirect.com/science/article/pii/S0169328X03001633?via%3Dihubrestricted access616-053.31CannabinoidsCB receptorsHypoxia–ischemiaBrain damageNewborn ratsCiencias Biomédicas24 Ciencias de la Vida