Suppression of glial activation is involved in the protection of IL-10 on maternal E. coli induced neonatal white matter injury

Pang, Yi; Rodts-Palenik, Sheryl; Cai, Zhengwei; Bennett, William A.; Rhodes, Philip

doi:10.1016/j.devbrainres.2005.03.015

Cited by 71 publications

(51 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…IL-10 is an anti-inflammatory cytokine capable of suppressing proinflammatory cytokine production and has been shown to have a protective effect on developing white matter [73,74,75]. However, our present data indicate that the possible protective effect of IL-10 might become overshadowed by the strong proinflammatory response induced by LPS.…”

Section: Discussioncontrasting

confidence: 55%

Development of Cerebral Gray and White Matter Injury and Cerebral Inflammation over Time after Inflammatory Perinatal Asphyxia

Bonestroo¹,

Heijnen²,

Groenendaal

et al. 2015

Dev Neurosci

View full text Add to dashboard Cite

Antenatal inflammation is associated with increased severity of hypoxic-ischemic (HI) encephalopathy and adverse outcome in human neonates and experimental rodents. We investigated the effect of lipopolysaccharide (LPS) on the timing of HI-induced cerebral tissue loss and gray matter injury, white matter injury and integrity, and the cerebral inflammatory response. On postnatal day 9, mice underwent HI by unilateral carotid artery occlusion followed by systemic hypoxia which resulted in early neuronal damage (MAP2 loss) at 3 h that did not increase up to day 15. LPS injection 14 h before HI (LPS+HI) significantly and gradually aggravated MAP2 loss from 3 h up to day 15, resulting in an acellular cystic lesion. LPS+HI increased white matter damage, reduced myelination in the corpus callosum and increased white matter fiber coherency in the cingulum. The number of oligodendrocytes throughout the lineage (Olig2-positive) was increased whereas more mature myelinating (CNPase-positive) oligodendrocytes were strongly decreased after LPS+HI. LPS+HI induced an increased and prolonged expression of cerebral cytokines/chemokines compared to HI. Additionally, LPS+HI increased macrophage/microglia activation and influx of neutrophils in the brain compared to HI. This study demonstrates the sensitizing effect of LPS on neonatal HI brain injury for an extended time-frame up to 15 days postinsult. LPS before HI induced a gradual increase in gray and white matter deficits, including reduced numbers of more mature myelinating oligodendrocytes and a decrease in white matter integrity. Moreover, LPS+HI prolonged and intensified the cerebral inflammatory response, including cellular infiltration. In conclusion, as the timing of damage and/or involved pathways are changed when HI is preceded by inflammation, experimental therapies might require modifications in the time window, dosage or combinations of therapies for efficacious neuroprotection.

show abstract

Section: Discussioncontrasting

confidence: 55%

Development of Cerebral Gray and White Matter Injury and Cerebral Inflammation over Time after Inflammatory Perinatal Asphyxia

Bonestroo¹,

Heijnen²,

Groenendaal

et al. 2015

Dev Neurosci

View full text Add to dashboard Cite

show abstract

“…In rats, Cai demonstrated activated caspase-3 cells within 24 h after intraventricular injection of LPS into neonatal brain [8]. Finally, several groups have demonstrated caspase-3 expression in pups on days 1 after LPS administration to pregnant females [33,39]. However, our data is the first to demonstrate that the initiator caspases are activated prior to the detection of the effector caspase (caspase-3).…”

Section: Caspases and Brain Injurysupporting

confidence: 46%

Caspase activation in fetal rat brain following experimental intrauterine inflammation

Sharangpani¹,

Takanohashi²,

Bell³

2008

Brain Research

View full text Add to dashboard Cite

Intrauterine inflammation has been implicated in developmental brain injuries, including the development of periventricular leukomalacia (PVL) and cerebral palsy (CP). Previous studies in our rat model of intrauterine inflammation demonstrated apoptotic cell death in fetal brains within the first 5 days after lipopolysaccharide (LPS) administration to mothers and eventual dysmyelination. Cysteine-containing, aspartate-specific proteases, or caspases, are proteins involved with apoptosis through both intracellular (intrinsic pathway) and extracellular (extrinsic pathway) mechanisms. We hypothesized that cell death in our model would occur mainly via activation of the extrinsic pathway. We further hypothesized that Fas, a member of the tumor necrosis factor receptor (TNFR) superfamily, would be increased and the death inducing signaling complex (DISC) would be detectable. Pregnant rats were injected intracervically with LPS at E15 and immunoblotting, immunohistochemical and immunoprecipitation analyses were performed. The presence of the activated form of the effector caspase (caspase-3) was observed 24 h after LPS administration. Caspase activity assays demonstrated rapid increases in (i) caspases-9 and -10 within 1 h, (ii) caspase-8 at 2 h and (iii) caspase-3 at 4 h. At 24 h after LPS, activated caspase-3 + /Fas + cells were observed within the developing white matter. Lastly, the DISC complex (caspase-8, Fas and Fasassociated Death Domain (FADD)) was observed within 30 min by immunoprecipitation. Apoptosis in our model occurs via both extrinsic and intrinsic pathways, and activation of Fas may play a role. Understanding the mechanisms of cell death in models of intrauterine inflammation may affect development of future strategies to mitigate these injuries in children.

show abstract

“…Suppression of macrophage/microglial activation has been proposed as a potential mechanism involved in the protective effect of IL-10 against maternal E. coli-induced neonatal white matter damage [219]. Alternatively, Sadowsky et al [65] proposed that the intravenous administration of IL-10, despite its rapid decay, may be important in targeting decidual macrophages.…”

Section: Il-10 Administration: Possible Implications In the Preventiomentioning

confidence: 99%

The anti-inflammatory limb of the immune response in preterm labor, intra-amniotic infection/inflammation, and spontaneous parturition at term: A role for interleukin-10

Gotsch

Romero

Kusanovic

et al. 2008

The Journal of Maternal-Fetal & Neonatal Medicine

119

View full text Add to dashboard Cite

Objective. The anti-inflammatory limb of the immune response is crucial for dampening inflammation. Spontaneous parturition at term and preterm labor (PTL) are mediated by inflammation in the cervix, membranes, and myometrium. This study focuses on the changes in the amniotic fluid concentrations of the anti-inflammatory cytokine interleukin (IL)-10. The objectives of this study were to determine whether there is a relationship between amniotic fluid concentrations of IL-10 and gestational age, parturition (at term and preterm), and intra-amniotic infection/inflammation (IAI). Study design. A cross-sectional study was conducted including 301 pregnant women in the following groups: (1) midtrimester of pregnancy who delivered at term (n ¼ 112); (2) mid-trimester who delivered preterm neonates (n ¼ 30); (3) term not in labor without IAI (n ¼ 40); (4) term in labor without IAI (n ¼ 24); (5) term in labor with IAI (n ¼ 20); (6) PTL without IAI who delivered at term (n ¼ 31); (7) PTL without IAI who delivered preterm (n ¼ 30); (8) PTL with IAI who delivered preterm (n ¼ 14). IL-10 concentrations in amniotic fluid were determined by a specific and sensitive immunoassay. Nonparametric statistics were used for analysis. Results.(1) IL-10 was detectable in amniotic fluid and its median concentration did not change with gestational age from mid-trimester to term. (2) Patients in labor at term had a significantly higher median amniotic fluid IL-10 concentration than that of patients at term not in labor (p ¼ 0.04). (3) Women at term in labor with IAI had a significantly higher median amniotic fluid IL-10 concentration than that of patients at term in labor without IAI (p ¼ 0.02). (4) Women with PTL and IAI who delivered preterm had a significantly higher median amniotic fluid concentration of IL-10 than those without IAI who delivered preterm and than those who delivered at term (p ¼ 0.009 and p 5 0.001, respectively). (5) Among patients with preterm labor without IAI, those who delivered preterm had a significantly higher median amniotic fluid IL-10 concentration than those who delivered at term (p ¼ 0.03). Conclusions. The anti-inflammatory cytokine IL-10 is detectable in the amniotic fluid of normal pregnant women. Spontaneous parturition at term and in preterm gestation is associated with increased amniotic fluid concentrations of IL-10. IAI (preterm and at term) is also associated with increased amniotic fluid concentrations of IL-10. We propose that IL-10 has a role in the regulation of the immune response in vivo by initiating actions that dampen inflammation.

show abstract

Suppression of glial activation is involved in the protection of IL-10 on maternal E. coli induced neonatal white matter injury

Cited by 71 publications

References 27 publications

Development of Cerebral Gray and White Matter Injury and Cerebral Inflammation over Time after Inflammatory Perinatal Asphyxia

Development of Cerebral Gray and White Matter Injury and Cerebral Inflammation over Time after Inflammatory Perinatal Asphyxia

Caspase activation in fetal rat brain following experimental intrauterine inflammation

The anti-inflammatory limb of the immune response in preterm labor, intra-amniotic infection/inflammation, and spontaneous parturition at term: A role for interleukin-10

Contact Info

Product

Resources

About