URB447 Is Neuroprotective in Both Male and Female Rats after Neonatal Hypoxia–Ischemia and Enhances Neurogenesis in Females

The need for new and effective treatments for neonates suffering from hypoxia–ischemia is urgent, as the only implemented therapy in clinics is therapeutic hypothermia, only effective in 50% of cases. Cannabinoids may modulate neuronal development and brain plasticity, but further investig...

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Detalhes bibliográficos
Autores: Beldarrain González, Gorane, Chillida Fibla, Marc, Hilario Rodríguez, Enrique, Herrero de la Parte, Borja, Álvarez Díaz, Antonia Ángeles, Alonso-Alconada, Daniel
Tipo de documento: artigo
Data de publicação:2024
País:España
Recursos:Universidad del País Vasco
Repositório:Addi. Archivo Digital para la Docencia y la Investigación
OAI Identifier:oai:addi.ehu.eus:10810/66589
Acesso em linha:http://hdl.handle.net/10810/66589
Access Level:Acceso aberto
Palavra-chave:neonatal hypoxia–ischemia
endocannabinoid system
neuroprotection
neurogenesis
Descrição
Resumo:The need for new and effective treatments for neonates suffering from hypoxia–ischemia is urgent, as the only implemented therapy in clinics is therapeutic hypothermia, only effective in 50% of cases. Cannabinoids may modulate neuronal development and brain plasticity, but further investigation is needed to better describe their implication as a neurorestorative therapy after neonatal HI. The cannabinoid URB447, a CB1 antagonist/CB2 agonist, has previously been shown to reduce brain injury after HI, but it is not clear whether sex may affect its neuroprotective and/or neurorestorative effect. Here, URB447 strongly reduced brain infarct, improved neuropathological score, and augmented proliferative capacity and neurogenic response in the damaged hemisphere. When analyzing these effects by sex, URB447 ameliorated brain damage in both males and females, and enhanced cell proliferation and the number of neuroblasts only in females, thus suggesting a neuroprotective effect in males and a double neuroprotective/neurorestorative effect in females.