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oai:docta.ucm.es:20.500.14352/1170722025-03-18T14:15:59Zcom_20.500.14352_14col_20.500.14352_15

Neuroprotection by the cannabinoid agonist WIN-55212 in an in vivo newborn rat model of acute severe asphyxia Martínez Orgado, José Antonio Fernádez Frutos, Beatriz González, Rita Romero, Eva Urigüen, Leire Romero, Julián Viveros Hernando, María Paz 616-053.31 Cannabinoids CB receptors Hypoxia–ischemia Brain damage Newborn rats Ciencias Biomédicas 24 Ciencias de la Vida This 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. Sociedad Española de Neonatología Depto. de Salud Pública y Materno - Infantil Fac. de Medicina TRUE pub 2025-01-30T07:30:25Z 2025-01-30T07:30:25Z 2003-06-10 journal article VoR https://hdl.handle.net/20.500.14352/117072 0169-328X 10.1016/s0169-328x(03)00163-3. eng PI021540/02 Martínez-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)00163-3 restricted access application/pdf Elsevier