RESUMO
Perinatal asphyxia remains a significant cause of neonatal mortality and is associated with long-term neurodegenerative disorders. In the present study, we evaluated cellular and subcellular damages to brain development in a model of mild perinatal asphyxia. Survival rate in the experimental group was 67%. One hour after the insult, intraperitoneally injected Evans blue could be detected in the fetuses' brains, indicating disruption of the blood-brain barrier. Although brain mass and absolute cell numbers (neurons and non-neurons) were not reduced after perinatal asphyxia immediately and in late brain development, subcellular alterations were detected. Cortical oxygen consumption increased immediately after asphyxia, and remained high up to 7 days, returning to normal levels after 14 days. We observed an increased resistance to mitochondrial membrane permeability transition, and calcium buffering capacity in asphyxiated animals from birth to 14 days after the insult. In contrast to ex vivo data, mitochondrial oxygen consumption in primary cell cultures of neurons and astrocytes was not altered after 1% hypoxia. Taken together, our results demonstrate that although newborns were viable and apparently healthy, brain development is subcellularly altered by perinatal asphyxia. Our findings place the neonate brain mitochondria as a potential target for therapeutic protective interventions.
Assuntos
Asfixia/patologia , Encéfalo/crescimento & desenvolvimento , Encéfalo/patologia , Mitocôndrias/patologia , Animais , Animais Recém-Nascidos , Asfixia/sangue , Astrócitos/metabolismo , Astrócitos/patologia , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/patologia , Encéfalo/metabolismo , Hipóxia Celular , Respiração Celular , Células Cultivadas , Citrato (si)-Sintase/metabolismo , Metabolismo Energético , Feminino , Lactatos/sangue , Potencial da Membrana Mitocondrial , Mitocôndrias/metabolismo , Membranas Mitocondriais/metabolismo , Neurônios/metabolismo , Neurônios/patologia , Tamanho do Órgão , Permeabilidade , Ratos Wistar , Análise de SobrevidaRESUMO
Alcohol intake during pregnancy has a tremendous impact on the developing brain. Embryonic and early postnatal alcohol exposures have been investigated experimentally to elucidate the fetal alcohol spectrum disorders' (FASD) milieu, and new data have emerged to support a devastating effect on the GABAergic system in the adult and developing nervous system. GABA is a predominantly inhibitory neurotransmitter that during development excites neurons and orchestrates several developmental processes such as proliferation, migration, differentiation, and synaptogenesis. This review summarizes and brings new data on neurodevelopmental aspects of the GABAergic system with FASD in experimental telencephalic models.