title: Sex-dependent consequences of neonatal brain hypoxia-ischemia in the rat.
abstract: Neonatal hypoxia-ischemia (HI) is an important cause of neurological deficits in humans, and the Levine-Rice model of experimental HI in the rat mimics the human brain lesion and the following sensory motor deficits and cognitive disabilities. With the growing evidence that sex influences all levels of brain functions, this Mini-Review highlights studies in which sex was a controlled variable and that provided evidence of sexual dimorphism in behavioral outcome, extension of brain damage, mechanisms of lesion, and treatment efficacy in the rat neonatal HI model. It was shown that 1) females have greater memory deficits; 2) cell death is dependent mainly on caspase activation in females; 3) males are more susceptible to oxidative stress; and 4) treatments acting on distinct cell death pathways afford sex-dependent neuroprotection. These tentative conclusions, along with growing evidence from other fields of neurobiology, support the need for scientists to design their experiments considering sex as an important variable; otherwise, important knowledge will continue to be missed. It is conceivable that sex can influence the development of efficacious therapeutic tools to treat neonates suffering from brain HI. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Biochemistry, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Carlos Alexandre
authors.initials: CA
authors.lastname: Netto
authors.affiliation: Division of Child Development and Growth, Department of Pediatrics, University of Geneva, Geneva, Switzerland.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Sanches
authors.affiliation: Postgraduate Program of Neurosciences, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Felipe Kawa
authors.initials: FK
authors.lastname: Odorcyk
authors.affiliation: Postgraduate Program of Physiology, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Luz Elena
authors.initials: LE
authors.lastname: Duran-Carabali
authors.affiliation: Department of Cellular Biology, Universidade de Brasília, Brasilia, Distrito Federal, Brazil.
authors.forename: Simone Nardin
authors.initials: SN
authors.lastname: Weis
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000473:pathology*; D002658:Developmental Disabilities / Q000209:etiology*; D004195:Disease Models, Animal; D005260:Female; D020925:Hypoxia-Ischemia, Brain / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051381:Rats; D012727:Sex Characteristics
keywords: cell death pathways; mitochondria; neonatal hypoxia-ischemia; sexual dimorphism