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American Academy of Pediatrics
Article

Intraventricular Hemorrhage and White Matter Injury in Preclinical and Clinical Studies

Olga Romantsik, Matteo Bruschettini and David Ley
NeoReviews November 2019, 20 (11) e636-e652; DOI: https://doi.org/10.1542/neo.20-11-e636
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Olga Romantsik
Department of Clinical Sciences Lund, Pediatrics, Lund University, Skane University Hospital, Lund, Sweden
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Matteo Bruschettini
Department of Clinical Sciences Lund, Pediatrics, Lund University, Skane University Hospital, Lund, Sweden
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David Ley
Department of Clinical Sciences Lund, Pediatrics, Lund University, Skane University Hospital, Lund, Sweden
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  • Abbreviations:
    A1M:
    alfa-1-microglobulin
    AQP1:
    aquaporin 1
    BBB:
    blood-brain barrier
    CPE:
    choroid plexus epithelium
    CSF:
    cerebrospinal fluid
    DFX:
    deferoxamine
    GM:
    germinal matrix
    GMH:
    germinal matrix hemorrhage
    hA1M:
    human plasma alfa-1-microglobulin
    Hb:
    hemoglobin
    Hp:
    haptoglobin
    ICH:
    intracranial hemorrhage
    IGF-1:
    insulinlike growth factor 1
    IVH:
    intraventricular hemorrhage
    MMP:
    matrix metalloproteinase
    MSC:
    mesenchymal stem cell
    NKCC:
    Na/K/Cl cotransporter
    PAR:
    protease-activated receptor
    PHVD:
    posthemorrhagic ventricular dilatation
    rA1M:
    recombinant human alfa-1-microglobulin
    rEPO:
    recombinant erythropoietin
    SPAK:
    Ste20-type stress kinase
    TGF-β:
    transforming growth factor β
    TLR:
    Toll-like receptor
    VEGF:
    vascular endothelial growth factor
    WM:
    white matter
  • Abstract

    Germinal matrix–intraventricular hemorrhage (IVH) occurs in nearly half of infants born at less than 26 weeks’ gestation. Up to 50% of survivors with IVH develop cerebral palsy, cognitive deficits, behavioral disorders, posthemorrhagic ventricular dilatation, or a combination of these sequelae. After the initial bleeding and the primary brain injury, inflammation and secondary brain injury might lead to periventricular leukomalacia or diffuse white matter injury. Potential factors that are involved include microglia and astrocyte activation, degradation of blood components with release of “toxic” products, infiltration of the brain by systemic immune cells, death of neuronal and glial cells, and arrest of preoligodendrocyte maturation. In addition, impairment of the blood-brain barrier may play a major role in the pathophysiology. A wide range of animal models has been used to explore causes and mechanisms leading to IVH-induced brain injury. Preclinical studies have identified potential targets for enhancing brain repair. However, little has been elucidated about the effectiveness of potential interventions in clinical studies. A systematic review of available preclinical and clinical studies might help identify research gaps and which types of interventions may be prioritized. Future trials should report clinically robust and long-term outcomes after IVH.

    • Copyright © 2019 by the American Academy of Pediatrics
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    NeoReviews
    Vol. 20, Issue 11
    1 Nov 2019
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    Intraventricular Hemorrhage and White Matter Injury in Preclinical and Clinical Studies
    Olga Romantsik, Matteo Bruschettini, David Ley
    NeoReviews Nov 2019, 20 (11) e636-e652; DOI: 10.1542/neo.20-11-e636

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    Intraventricular Hemorrhage and White Matter Injury in Preclinical and Clinical Studies
    Olga Romantsik, Matteo Bruschettini, David Ley
    NeoReviews Nov 2019, 20 (11) e636-e652; DOI: 10.1542/neo.20-11-e636
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    • Article
      • Abstract
      • Education Gaps
      • Objectives
      • INTRODUCTION
      • IVH MODELING
      • PREVENTION
      • GM-IVH–INDUCED BRAIN INJURY
      • PRECLINICAL FINDINGS ON REPAIR OF INJURY
      • CONCLUSIONS
      • Footnotes
      • References
    • Figures & Data
    • Info & Metrics
    • Comments

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