Trends in severe brain injury and neurodevelopmental outcome in premature newborn infants: The role of cystic periventricular leukomalacia

Hamrick, Shannon E. G.; Miller, Steven P.; Leonard, Carol H.; Glidden, David V.; Goldstein, Ruth B.; Ramaswamy, Vijay; Piecuch, Robert E.; Ferriero, Donna M.

doi:10.1016/j.jpeds.2004.05.042

Cited by 285 publications

(190 citation statements)

References 23 publications

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“…Interestingly, the clinically evident decline in cystic PVL rates in recent years (Hamrick et al, 2004) has been accompanied by a decrease in days of mechanical ventilation. However, this decline was not associated with improved developmental outcome, indicating that other forms of cerebral injury contribute to abnormal neurodevelopmental outcomes in premature infants (Hamrick et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

“…Two major causes are generally considered to be responsible for perinatal white matter injury: cerebral ischemia/reperfusion in the premature infant, combined with the propensity for impaired vascular autoregulation (Menke et al, 1997;Volpe, 1998) and bacterial infection in the mother and/or fetus that triggers a cytokine response in the fetal brain (Kinney et al, 2004;Leviton and Dammann, 2004). In the past 10 years, there has been no improvement in the neurodevelopmental outcome of premature infants (Hamrick et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

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Hyperoxia Causes Maturation-Dependent Cell Death in the Developing White Matter

Gerstner

DeSilva²,

Genz³

et al. 2008

J. Neurosci.

160

145

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Periventricular leukomalacia is the predominant injury in the preterm infant leading to cerebral palsy. Oxygen exposure may be an additional cause of brain injury in these infants. In this study, we investigated pathways of maturation-dependent oligodendrocyte (OL) death induced by hyperoxia in vitro and in vivo. Developing and mature OLs were subjected to 80% oxygen (0 -24 h). Lactate dehydrogenase (LDH) assay was used to assess cell viability. Furthermore, 3-, 6-, and 10-d-old rat pups were subjected to 80% oxygen (24 h), and their brains were processed for myelin basic protein staining. Significant cell death was detected after 6 -24 h incubation in 80% oxygen in pre-OLs (O4ϩ,O1Ϫ), but not in mature OLs (MBPϩ). Cell death was executed by a caspase-dependent apoptotic pathway and could be blocked by the pan-caspase inhibitor zVAD-fmk. Overexpression of BCL2 (Homo sapiens B-cell chronic lymphocytic leukemia/lymphoma 2) significantly reduced apoptosis. Accumulation of superoxide and generation of reactive oxygen species (ROS) were detected after 2 h of oxygen exposure. Lipoxygenase inhibitors 2,3,5-trimethyl-6-(12-hydroxy-5-10-dodecadiynyl-1,4-benzoquinone and N-benzyl-N-hydroxy-5-phenylpentamide fully protected the cells from oxidative injury. Overexpression of superoxide dismutase (SOD1) dramatically increased injury to pre-OLs but not to mature OLs. We extended these studies by testing the effects of hyperoxia on neonatal white matter. Postnatal day 3 (P3) and P6 rats, but not P10 pups, showed bilateral reduction in MBP (myelin basic protein) expression with 24 h exposure to 80% oxygen. Hyperoxia causes oxidative stress and triggers maturation-dependent apoptosis in pre-OLs, which involves the generation of ROS and caspase activation, and leads to white matter injury in the neonatal rat brain. These observations may be relevant to white matter injury observed in premature infants.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Hyperoxia Causes Maturation-Dependent Cell Death in the Developing White Matter

Gerstner

DeSilva²,

Genz³

et al. 2008

J. Neurosci.

160

145

View full text Add to dashboard Cite

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“…Periventricular white matter injury (PWMI) can range from focal cystic necrotic lesions of cerebral white matter (periventricular leukomalacia, PVL) to diffuse damage of myelin. Because of advances in neonatal care, cystic necrotic lesions of PVL are declining, 67 and focal or diffuse WMI is now the predominant lesion clinically observed. Both cystic PVL and diffuse white matter disease are characterized by reduced white matter volume, reduced brain growth and features, suggesting abnormal myelination by magnetic resonance imaging.…”

Section: Ols and Diseasementioning

confidence: 99%

Maturation-dependent sensitivity of oligodendrocyte lineage cells to apoptosis: implications for normal development and disease

2008

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Apoptosis plays a crucial role in brain development by ensuring that only appropriately growing, migrating, and synapse-forming neurons and their associated glial cells survive. This process involves an intimate relationship between cell-cell interactions and developmental cues and is further impacted by environmental stress during neurogenesis and disease. Oligodendrocytes (OLs), the major myelin-forming cells in the central nervous system, largely form after this wave of neurogenesis but also show a selective vulnerability to cell death stimuli depending on their stage of development. This can affect not only embryonic and early postnatal brain formation but also the response to demyelinating pathologies. In the present review, we discuss the stagespecific sensitivity of OL lineage cells to damage-induced death and how this might impact myelin survival and regeneration during injury or disease. Apoptosis is a major form of programmed cell death required for the normal development of metazoan tissues, including the brain. 1 During embryonic development of the brain, many more cells than ultimately needed are generated and then selection occurs, resulting in the apoptotic depletion of the surplus cells. The importance of the apoptotic pathway in early brain development has been demonstrated by the targeted deletion in mice of the death-specific cysteine proteases caspase-3 or caspase-9, or of the co-activator Apaf-1, all of which cause severe brain overgrowth and perinatal death. 2,3 In the adult brain, 90% of the cells belong to the glial lineage, which includes oligodendrocytes (OLs), astrocytes and microglia. The glia ensures proper development, function and repair of the neuronal network. This is possible through continuous cross-talk between the glia and neurons mediated by neurotransmitters, cytokines, growth and trophic factor secretion and signaling in a reciprocal manner. [4][5][6][7] In the central nervous system (CNS), OLs are responsible for axon myelination, which insulates the electrical signals transmitted between neurons. OL and neuron development is tightly regulated and the myelin sheath is constructed only when OLs reach maturity and neurons have grown appropriately. In response to injury or during the course of neurological diseases, the neuron-glia network can be replenished to some extent but the degree of repair is dependent on the developmental stage of the OL. This complexity is compounded by the differential sensitivity of OL lineage cells to apoptotic stimuli. In the present review, we will first briefly examine the stages of differentiation of OL cells and then discuss several diseases that are impacted by OL apoptosis, noting how the stage of cell differentiation governs the sensitivity to apoptosis. Defined Stages of OL DevelopmentOligodendrocyte development can be divided into four distinct stages according to the temporal expression of cell surface markers and morphology (Table 1). 8 In the first stage, OL progenitor cells (OPCs) originate from the neuroepithelium of the ventricul...

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“…Up to 20% of these infants develop cerebral palsy (Hamrick et al, 2004); an additional 25% to 50% experience attention deficit disorder, learning disabilities, or visual cortical impairments (Litt et al, 2005). This group also has a higher incidence of psychiatric morbidities (Johnson, 2007).…”

Section: Introductionmentioning

confidence: 99%

In vivo Magnetization Transfer MRI Shows Dysmyelination in an Ischemic Mouse Model of Periventricular Leukomalacia

Fatemi

Wilson

Phillips

et al. 2011

J Cereb Blood Flow Metab

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Periventricular leukomalacia, PVL, is the leading cause of cerebral palsy in prematurely born infants, and therefore more effective interventions are required. The objective of this study was to develop an ischemic injury model of PVL in mice and to determine the feasibility of in vivo magnetization transfer (MT) magnetic resonance imaging (MRI) as a potential monitoring tool for the evaluation of disease severity and experimental therapeutics. Neonatal CD-1 mice underwent unilateral carotid artery ligation on postnatal day 5 (P5); at P60, in vivo T2-weighted (T2w) and MT-MRI were performed and correlated with postmortem histopathology. In vivo T2w MRI showed thinning of the right corpus callosum, but no significant changes in hippocampal and hemispheric volumes. Magnetization transfer MRI revealed significant white matter abnormalities in the bilateral corpus callosum and internal capsule. These quantitative MT-MRI changes correlated highly with postmortem findings of reduced myelin basic protein in bilateral white matter tracts. Ventriculomegaly and persistent astrogliosis were observed on the ligated side, along with evidence of axonopathy and fewer oligodendrocytes in the corpus callosum. We present an ischemia-induced mouse model of PVL, which has pathologic abnormalities resembling autopsy reports in infants with PVL. We further validate in vivo MRI techniques as quantitative monitoring tools that highly correlate with postmortem histopathology.

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Trends in severe brain injury and neurodevelopmental outcome in premature newborn infants: The role of cystic periventricular leukomalacia

Cited by 285 publications

References 23 publications

Hyperoxia Causes Maturation-Dependent Cell Death in the Developing White Matter

Hyperoxia Causes Maturation-Dependent Cell Death in the Developing White Matter

Maturation-dependent sensitivity of oligodendrocyte lineage cells to apoptosis: implications for normal development and disease

In vivo Magnetization Transfer MRI Shows Dysmyelination in an Ischemic Mouse Model of Periventricular Leukomalacia

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