Systemic inflammation disrupts the developmental program of white matter.
Objective: Perinatal inflammation is a major risk factor for neurological deficits in preterm infants. Several experimental studies have shown that systemic inflammation can alter the programming of the developing brain. However, these studies do not offer detailed pathophysiological mechanisms, and...
| Publicado en: | Annals of Neurology Vol. 70; no. 4; pp. 550 - 566 |
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| Autores principales: | , , , , , , , , , , , , , , , , , , , |
| Formato: | research Journal Article |
| Publicado: |
Wiley-Blackwell
2011 Oct
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=108198876&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 108198876 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 03645134 1WM jtl: Annals of Neurology issn: 03645134 maglogo: Y pubinfo: dt: 2011 Oct vid: 70 iid: 4 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 108198876 108198876 NLM21796662 2011338446 10.1002/ana.22489 NLM21796662 108198876 ppf: 550 ppct: 16 formats: tig: atl: Systemic inflammation disrupts the developmental program of white matter. aug: au: Favrais G van de Looij Y Fleiss B Ramanantsoa N Bonnin P Stoltenburg-Didinger G Lacaud A Saliba E Dammann O Gallego J Sizonenko S Hagberg H Lelièvre V Gressens P Favrais, Géraldine van de Looij, Yohan Fleiss, Bobbi Ramanantsoa, Nelina Bonnin, Philippe Stoltenburg-Didinger, Gisela affil: INSERM U676, Denis Diderot Faculty of Medicine, University of Paris 7, Paris, France sug: subj: Brain Inflammation Pathology Interleukin 1 Pharmacodynamics Magnetic Resonance Imaging Nerve Fibers Pathology Central Nervous System Pathology Animal Studies Animal Population Groups Brain Drug Effects Brain Pathology Injections Interleukin 1 Administration and Dosage Mice Nerve Fibers Drug Effects Central Nervous System Drug Effects Funding Source ab: Objective: Perinatal inflammation is a major risk factor for neurological deficits in preterm infants. Several experimental studies have shown that systemic inflammation can alter the programming of the developing brain. However, these studies do not offer detailed pathophysiological mechanisms, and they rely on relatively severe infectious or inflammatory stimuli that most likely do not reflect the levels of systemic inflammation observed in many human preterm infants. The goal of the present study was to test the hypothesis that moderate systemic inflammation is sufficient to alter white matter development.Methods: Newborn mice received twice-daily intraperitoneal injections of interleukin-1β (IL-1β) over 5 days and were studied for myelination, oligodendrogenesis, and behavior and with magnetic resonance imaging (MRI).Results: Mice exposed to IL-1β had a long-lasting myelination defect that was characterized by an increased number of nonmyelinated axons. They also displayed a reduction of the diameter of the myelinated axons. In addition, IL-1β induced a significant reduction of the density of myelinating oligodendrocytes accompanied by an increased density of oligodendrocyte progenitors, suggesting a partial blockade in the oligodendrocyte maturation process. Accordingly, IL-1β disrupted the coordinated expression of several transcription factors known to control oligodendrocyte maturation. These cellular and molecular abnormalities were correlated with a reduced white matter fractional anisotropy on diffusion tensor imaging and with memory deficits.Interpretation: Moderate perinatal systemic inflammation alters the developmental program of the white matter. This insult induces a long-lasting myelination deficit accompanied by cognitive defects and MRI abnormalities, further supporting the clinical relevance of the present data. pubtype: Academic Journal doctype: research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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