Activated protein C reduces endotoxin-induced white matter injury in the developing rat brain

Yesilirmak, Didem Cemile; Kumral, Abdullah; Baskın, Hüseyin; Ergur, Bekir Uğur; Aykan, Simge; Genç, Şermin; Genç, Kürşad; Yılmaz, Osman; Tugyan, Kazim; Giray, Özlem; Duman, Nuray; Özkan, Hasan

doi:10.1016/j.brainres.2007.04.083

Cited by 26 publications

(21 citation statements)

References 69 publications

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“…3b). The data imply a white matter injury morphology in the LPS groups39. These characteristics are obvious at 25 μg/kg LPS, and NAC inhibited these changes.…”

Section: Resultsmentioning

confidence: 69%

“…N-acetyl-cysteine (NAC), a non-specific free radical scavenger and NF-κB inhibitor, reduces maternal serum LPS-induced oxidative stress and the proinflammatory cytokines TNF-α, IL-6, and IL-1β353637. This provides protective effects against fetal death and preterm labor33, apoptotic white matter loss, and learning and behavioral deficits3839. In this study, we examined whether NAC application protects fetal brain development from maternal LPS-induced oxidative damage.…”

mentioning

confidence: 99%

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N-acetylcysteine attenuates lipopolysaccharide-induced impairment in lamination of Ctip2-and Tbr1- expressing cortical neurons in the developing rat fetal brain

Chao

Chen

Yang

et al. 2016

Sci Rep

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Oxidative stress and inflammatory insults are the major instigating events of bacterial intrauterine infection that lead to fetal brain injury. The purpose of this study is to investigate the remedial effects of N-acetyl-cysteine (NAC) for inflammation-caused deficits in brain development. We found that lipopolysaccharide (LPS) induced reactive oxygen species (ROS) production by RAW264.7 cells. Macrophage-conditioned medium caused noticeable cortical cell damage, specifically in cortical neurons. LPS at 25 μg/kg caused more than 75% fetal loss in rats. An increase in fetal cortical thickness was noted in the LPS-treated group. In the enlarged fetal cortex, laminar positioning of the early born cortical cells expressing Tbr1 and Ctip2 was disrupted, with a scattered distribution. The effect was similar, but minor, in later born Satb2-expressing cortical cells. NAC protected against LPS-induced neuron toxicity in vitro and counteracted pregnancy loss and alterations in thickness and lamination of the neocortex in vivo. Fetal loss and abnormal fetal brain development were due to LPS-induced ROS production. NAC is an effective protective agent against LPS-induced damage. This finding highlights the key therapeutic impact of NAC in LPS-caused abnormal neuronal laminar distribution during brain development.

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“…3b). The data imply a white matter injury morphology in the LPS groups39. These characteristics are obvious at 25 μg/kg LPS, and NAC inhibited these changes.…”

Section: Resultsmentioning

confidence: 69%

mentioning

confidence: 99%

N-acetylcysteine attenuates lipopolysaccharide-induced impairment in lamination of Ctip2-and Tbr1- expressing cortical neurons in the developing rat fetal brain

Chao

Chen

Yang

et al. 2016

Sci Rep

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“…The action of APC depends on binding to EPCR, which acts in concert with thrombomodulin. APC reduced lipopolysaccharide-induced white matter injury in fetal rat brain 23 and has been proposed as treatment for perinatal white matter injury. 24 The tested EPCR variant was not associated with a specific CP subtype.…”

Section: Discussionmentioning

confidence: 99%

Candidate Genes and Cerebral Palsy: A Population-Based Study

Gibson¹,

MacLennan²,

Dekker³

et al. 2008

Pediatrics

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Two of the 28 single-nucleotide polymorphisms examined were associated with all types of spastic cerebral palsy in both gestational age groups and others with cerebral palsy in gestational age or cerebral palsy subgroups. Some of these associations support previous findings. There may be a genetic contribution to cerebral palsy risk, and additional investigation is warranted of genes and gene-environment interactions in cerebral palsy.

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“…The pathogenesis of PVL is multi-factorial and likely involves in ischemia-reperfusion, formation of reactive oxygen and nitrogen species, glutamate exitotoxicity, impairment of myelination due to loss of oligodendrocytes, apoptotic cell death, microglial activation, and maternal or fetal infection (Adams-Chapman, 2006; Leviton and Dammann, 2004). PVL is known as the major antecedent disorder developing to CP (Yesilirmak et al, 2007). Several animal models have been established to study the mechanisms of PVL and to search the therapeutic potential of candidate agents (Adams-Chapman, 2006).…”

Section: Discussionmentioning

confidence: 99%

“…Approximately 10% of newborns are born prematurely, and severe disturbances in mental development and perinatal brain injuries have been observed in premature infants (Yesilirmak et al, 2007). More than 10% of these children have adverse neurological outcomes, including cognitive, motor, and behavioral deficits (Wozniak et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Effects of endurance exercise on expressions of glial fibrillary acidic protein and myelin basic protein in developing rats with maternal infection-induced cerebral palsy

Kim¹,

Shin

Cho

et al. 2014

J Exerc Rehabil

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Periventricular leukomalacia (PVL) is a common white matter lesion affecting the neonatal brain. PVL is closely associated with cerebral palsy (CP) and characterized by increase in the number of astrocytes, which can be detected by positivity for glial fibrillary acidic protein (GFAP). Change in myelin basic protein (MBP) is an early sign of white matter abnormality. Maternal or placental infection can damage the neonatal brain. In the present study, we investigated the effects of treadmill walking exercise on GFAP and MBP expressions in rats with maternal lipopolysaccharide (LPS)-induced PVL. Immunohistochemistry was performed for the detection of GFAP and MBP. The present results showed that intracervical maternal LPS injection during pregnancy increased GFAP expression in the striatum and decreased MBP expression in the corpus callosum of rats. The results also showed that treadmill walking exercise suppressed GFAP expression and enhanced MBP expression in the brains of rats with maternal LPS-induced PVL. The present study revealed that treadmill walking exercise is effective for the suppressing astrogliosis and hypomyelination associated with PVL. Here in this study, we showed that treadmill walking exercise may be effective therapeutic strategy for alleviating the detrimental effects of CP.

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Activated protein C reduces endotoxin-induced white matter injury in the developing rat brain

Cited by 26 publications

References 69 publications

N-acetylcysteine attenuates lipopolysaccharide-induced impairment in lamination of Ctip2-and Tbr1- expressing cortical neurons in the developing rat fetal brain

N-acetylcysteine attenuates lipopolysaccharide-induced impairment in lamination of Ctip2-and Tbr1- expressing cortical neurons in the developing rat fetal brain

Candidate Genes and Cerebral Palsy: A Population-Based Study

Effects of endurance exercise on expressions of glial fibrillary acidic protein and myelin basic protein in developing rats with maternal infection-induced cerebral palsy

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