Amniotic fluid inflammatory cytokines (interleukin-6, interleukin-1β, and tumor necrosis factor-α), neonatal brain white matter lesions, and cerebral palsy

Yoon, Bo Hyun; Jun, Jong Kwan; Romero, Roberto; Park, Kyo Hoon; Gomez, Ricardo; Choi, Jung‐Hwan; Kim, In-One

doi:10.1016/s0002-9378(97)70432-0

Cited by 757 publications

(495 citation statements)

References 24 publications

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“…Maternal LPS exposure has been shown to stimulate the secretion of pro-inflammatory cytokines i.e., TNF-α, IL-1α and IL-6 in the maternal serum and amniotic fluid of pregnant mice (Fidel et al, 1994) mimicking maternal infection (Yoon et al, 1997). Results presented here describe the role of peroxisomes in prenatal maternal infection (LPS)-induced cerebral white matter injury.…”

Section: Discussionmentioning

confidence: 82%

“…Also, maternal injection of LPS at embryonic gestation day 18 (E18) and E19 increases pro-inflammatory cytokine (TNF-α and IL-1β) expression in the maternal and fetal compartments including fetal brain (Cai et al, 2000;Wang et al, 2006). Secretion of proinflammatory cytokines in the amniotic fluid arising from intrauterine infection is shown to be associated with brain white matter injury (Yoon et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

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Lipopolysaccharide-induced peroxisomal dysfunction exacerbates cerebral white matter injury: Attenuation by N-acetyl cysteine

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Contreras

et al. 2008

Experimental Neurology

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Cerebral white matter injury during prenatal maternal infection characterized as periventricular leukomalacia (PVL) is the main substrate for cerebral palsy (CP) in premature infants. Previously, we reported that maternal LPS exposure causes oligodendrocyte (OL)-injury/hypomyelination in the developing brain which can be attenuated by an antioxidant agent, N-acetyl cysteine (NAC). Herein, we elucidated the role of peroxisomes in LPS-induced neuroinflammation and cerebral white matter injury. Peroxisomes are important for detoxification of reactive oxidative species (ROS) and metabolism of myelin-lipids in OLs. Maternal LPS exposure induced selective depletion of developing OLs in the fetal brain which was associated with ROS generation, glutathione depletion and peroxisomal dysfunction. Likewise, hypomyelination in the postnatal brain was associated with decrease in peroxisomes in OLs after maternal LPS exposure. Conversely, NAC abolished these LPS-induced effects in the developing brain. CP brains imitated these changes in peroxisomal/myelin proteins in the postnatal brain after maternal LPS exposure. In vitro studies revealed that proinflammatory cytokines cause OL-injury via peroxisomal dysfunction and ROS generation. NAC or WY14643 (peroxisome proliferators activated receptor (PPAR)-α agonist) reverses these effects of proinflammatory cytokines in the wild-type OLs, but not in PPAR-α (−/−) OLs. Similarly treated B12 oligodenroglial cells co-transfected with PPAR-α siRNAs/pTK-PPREx3-Luc, and LPS exposed PPAR-α (−/−) pregnant mice treated with NAC or WY14643 further suggested that PPAR-α activity mediates NAC-induced protective effects. Collectively, these data provide unprecedented evidence that LPS-induced peroxisomal dysfunction exacerbates cerebral white matter injury and NACinduced protection is via a PPAR-α dependent mechanism expands therapeutic avenues for PVL and related demyelinating diseases.

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Section: Discussionmentioning

confidence: 82%

Section: Introductionmentioning

confidence: 99%

Lipopolysaccharide-induced peroxisomal dysfunction exacerbates cerebral white matter injury: Attenuation by N-acetyl cysteine

Paintlia

Contreras

et al. 2008

Experimental Neurology

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“…[85][86][87] Furthermore, in full-term newborn infants 88 and in animal models, 89 the combined exposure of infection and HI dramatically increases the risk of cerebral palsy and brain injury, 88 suggesting an interaction between systemic infections and HI. Increased concentrations of inflammatory cytokines in umbilical cord blood are associated with cerebral lesions in pre-term infants.…”

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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“…High interleukin (IL)-6 and IL-1␤ concentrations in amniotic fluid have been found in preterm infants with white matter (WM) lesions (1), and elevated IL-6, IL-8, and IL-1 ␤ levels in both umbilical and neonatal blood samples of preterm infants have been found to associate with intracerebral hemorrhage (2,3). Furthermore, in term infants, higher blood levels of IL-6, IL-8, and IL-1 ␤ have been reported to associate with abnormal neurodevelopmental outcome at 30 mo of age (4).…”

mentioning

confidence: 99%

Interleukin-6 -174 and -572 Genotypes and the Volume of Deep Gray Matter in Preterm Infants

et al. 2009

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Preterm infants have smaller cerebral and cerebellar volumes at term compared with term born infants. Perinatal factors leading to the reduction in volumes are not well known. IL-6 -174 and -572 genotypes partly regulate individual immunologic responses and have also been connected with deviant neurologic development in preterm infants. Our hypothesis was that IL-6 -174 and -572 genetic polymorphisms are associated with brain lesions and regional brain volumes in very low birth weight or in very preterm infants. DNA was genotyped for IL-6 -174 and -572 polymorphisms (GG/GC/CC). Study infants (n ϭ 175) were categorized into three groups according to the most pathologic brain finding in ultrasound examinations until term. The brain MRI performed at term was analyzed for regional brain volumes. Analyzed IL-6 genotypes did not show statistically significant association with structural brain lesions. However, IL-6 -174 CC and -572 GG genotypes associated with reduced volume of one brain region, the combined volume of basal ganglia and thalami, both in univariate and in multivariate analyses (p ϭ 0.009, 0.009, respectively). The association of IL-6 -174 and -572 genetic polymorphisms with smaller volumes in deep gray matter provides us new ways to understand the processes leading to neurologic impairments in preterm infants.

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Amniotic fluid inflammatory cytokines (interleukin-6, interleukin-1β, and tumor necrosis factor-α), neonatal brain white matter lesions, and cerebral palsy

Cited by 757 publications

References 24 publications

Lipopolysaccharide-induced peroxisomal dysfunction exacerbates cerebral white matter injury: Attenuation by N-acetyl cysteine

Lipopolysaccharide-induced peroxisomal dysfunction exacerbates cerebral white matter injury: Attenuation by N-acetyl cysteine

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

Interleukin-6 -174 and -572 Genotypes and the Volume of Deep Gray Matter in Preterm Infants

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