title: Glial response to 17β-estradiol in neonatal rats with excitotoxic brain injury.
abstract: White-matter injury is the most common cause of the adverse neurodevelopmental outcomes observed in preterm infants. Only few options exist to prevent perinatal brain injury associated to preterm delivery. 17β-estradiol (E2) is the predominant estrogen in circulation and has been shown to be neuroprotective in vitro and in vivo. However, while E2 has been found to modulate inflammation in adult models of brain damage, how estrogens influence glial cells response in the developing brain needs further investigations. Using a model of ibotenate-induced brain injury, we have refined the effects of E2 in the developing brain. E2 provides significant neuroprotection both in the cortical plate and the white matter in neonatal rats subjected to excitotoxic insult mimicking white matter and cortical damages frequently observed in very preterm infants. E2 promotes significant changes in microglial phenotypes balance in response to brain injury and the acceleration of oligodendrocyte maturation. Maturational effects of E2 on myelination process were observed both in vivo and in vitro. Altogether, these data demonstrate that response of glial cells to E2 could be responsible for its neuroprotective properties in neonatal excitotoxic brain injury.
authors.affiliation: Inserm, UMR1141, 75019 Paris, France; Université Paris Diderot, Faculté de Médecine, 75018 Paris, France; PremUP Foundation, 75014 Paris, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Pansiot
authors.affiliation: Inserm, UMR1141, 75019 Paris, France; PremUP Foundation, 75014 Paris, France.
authors.forename: Hoa
authors.initials: H
authors.lastname: Pham
authors.affiliation: Inserm, UMR1141, 75019 Paris, France; PremUP Foundation, 75014 Paris, France.
authors.forename: Jeremie
authors.initials: J
authors.lastname: Dalous
authors.affiliation: Université Paris Diderot, Faculté de Médecine, 75018 Paris, France; Assistance Publique - Hôpitaux de Paris, Hôpital Robert Debré, Department of Biochemistry and Hormonology, 75019 Paris, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Chevenne
authors.affiliation: Neonatal Intensive Care Unit, Istituto Giannina Gaslini, Genoa, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Colella
authors.affiliation: Inserm, UMR1141, 75019 Paris, France; Université Paris Diderot, Faculté de Médecine, 75018 Paris, France.
authors.forename: Leslie
authors.initials: L
authors.lastname: Schwendimann
authors.affiliation: Inserm, UMR1141, 75019 Paris, France.
authors.forename: Assia
authors.initials: A
authors.lastname: Fafouri
authors.affiliation: Inserm, UMR1141, 75019 Paris, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Mairesse
authors.affiliation: Inserm, UMR1141, 75019 Paris, France; S. Maria della Misericordia Hospital, Università degli studi di Udine, Udine, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Moretti
authors.affiliation: Inserm, UMR1141, 75019 Paris, France.
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Schang
authors.affiliation: Inserm, UMR1141, 75019 Paris, France.
authors.forename: Christiane
authors.initials: C
authors.lastname: Charriaut-Marlangue
authors.affiliation: Inserm, UMR1141, 75019 Paris, France; Université Paris Diderot, Faculté de Médecine, 75018 Paris, France; PremUP Foundation, 75014 Paris, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Gressens
authors.affiliation: Inserm, UMR1141, 75019 Paris, France; Université Paris Diderot, Faculté de Médecine, 75018 Paris, France; PremUP Foundation, 75014 Paris, France; Assistance Publique - Hôpitaux de Paris, Hôpital Robert Debré, Neonatal Intensive Care Unit, 75019 Paris, France. Electronic address: olivier.baud@rdb.aphp.fr.
authors.forename: Olivier
authors.initials: O
authors.lastname: Baud
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D004958:Estradiol / Q000494:pharmacology / Q000627:therapeutic use*; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D007051:Ibotenic Acid / Q000633:toxicity; D056784:Leukoencephalopathies / Q000139:chemically induced / Q000628:therapy*; D004676:Myelin Basic Protein / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009457:Neuroglia / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000076104:Oligodendrocyte Transcription Factor 2; D037121:Plant Lectins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D025601:Adenomatous Polyposis Coli Protein; D051792:Basic Helix-Loop-Helix Proteins; D016207:Cytokines; D004958:Estradiol; D018690:Excitatory Amino Acid Agonists; D007051:Ibotenic Acid; D004676:Myelin Basic Protein; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D000076104:Oligodendrocyte Transcription Factor 2; D037121:Plant Lectins; C522729:Olig2 protein, rat; C034981:tomato lectin
keywords: Estradiol; Excitoxicity; Neonate; Neuro-inflammation; Neuroprotection; White matter damage