title: A1 adenosine receptors mediate hypoxia-induced ventriculomegaly.
abstract: Periventricular leukomalacia is characterized by a reduction in brain matter and secondary ventriculomegaly and is a major cause of developmental delay and cerebral palsy in prematurely born infants. Currently, our understanding of the pathogenesis of this condition is limited. In animal models, features of periventricular leukomalacia can be induced by hypoxia and activation of A1 adenosine receptors (A1ARs). Using mice that are deficient in the A1AR gene (A1AR-/-), we show that A1ARs play a prominent role in the development of hypoxia-induced ventriculomegaly in neonates. Supporting a role for adenosine in the pathogenesis of developmental brain injury, ventriculomegaly was also observed in mice lacking the enzyme adenosine deaminase, which degrades adenosine. Thus, adenosine acting on A1ARs appears to mediate hypoxia-induced brain injury ventriculomegaly during early postnatal development.
authors.affiliation: Department of Pediatrics, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Turner
authors.forename: Meltem
authors.initials: M
authors.lastname: Seli
authors.forename: Laura
authors.initials: L
authors.lastname: Ment
authors.forename: William
authors.initials: W
authors.lastname: Stewart
authors.forename: Henglin
authors.initials: H
authors.lastname: Yan
authors.forename: Bjorn
authors.initials: B
authors.lastname: Johansson
authors.forename: Bertil B
authors.initials: BB
authors.lastname: Fredholm
authors.forename: Michael
authors.initials: M
authors.lastname: Blackburn
authors.forename: Scott A
authors.initials: SA
authors.lastname: Rivkees
mesh_terms: D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D017931:DNA Primers; D005838:Genotype; D006801:Humans; D000860:Hypoxia / Q000150:complications*; D007231:Infant, Newborn; D007969:Leukomalacia, Periventricular / Q000209:etiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D043682:Receptor, Adenosine A1 / Q000235:genetics / Q000502:physiology*
chemical_list: D017931:DNA Primers; D043682:Receptor, Adenosine A1