TNF-α antagonist attenuates systemic lipopolysaccharide-induced brain white matter injury in neonatal rats
Abstract Background Systemic inflammation is an important risk factor for neurodevelopmental impairments in preterm infants. Premyelinating oligodendrocytes are main building blocks of white matter in preterm infants and vulnerable to oxidative stress and excitotoxic stress. Tumour necrosis factor-α...
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doaj-4624f7497ff24ca586f0fb8cd6c54a322020-11-25T03:35:00ZengBMCBMC Neuroscience1471-22022019-08-012011910.1186/s12868-019-0529-1TNF-α antagonist attenuates systemic lipopolysaccharide-induced brain white matter injury in neonatal ratsSeung Han Shin0Ee-Kyung Kim1Kyung-yup Lee2Han-Suk Kim3Department of Pediatrics, Seoul National University College of Medicine, Seoul National University Children’s HospitalDepartment of Pediatrics, Seoul National University College of Medicine, Seoul National University Children’s HospitalDepartment of Pediatrics, Seoul National University College of Medicine, Seoul National University Children’s HospitalDepartment of Pediatrics, Seoul National University College of Medicine, Seoul National University Children’s HospitalAbstract Background Systemic inflammation is an important risk factor for neurodevelopmental impairments in preterm infants. Premyelinating oligodendrocytes are main building blocks of white matter in preterm infants and vulnerable to oxidative stress and excitotoxic stress. Tumour necrosis factor-α (TNF-α) plays important roles in systemic inflammation and local inflammation leading to apoptosis of premyelinating oligodendrocytes and white matter injury (WMI) in brain tissue. This study was conducted to investigate whether etanercept, a TNF-α antagonist, could attenuate systemic lipopolysaccharide (LPS)-induced WMI in the immature brain. Results We found that intraperitoneal LPS administration caused systemic and local inflammation in brain tissue. Subsequent etanercept treatment significantly attenuated LPS-induced inflammation in brain tissue as well as in systemic circulation. Intraperitoneal LPS also induced microgliosis and astrocytosis in the cingulum and etanercept treatment reduced LPS-induced microgliosis and astrocytosis. Additionally, systemic LPS-induced apoptosis of oligodendrocyte precursor cells was observed, which was lessened by etanercept treatment. The concentration of etanercept in the CSF was higher when it was administrated with LPS than when administrated with a vehicle. Conclusions It appears that etanercept reduce WMI in the neonatal rat brain via attenuation of systemic and local inflammation. This study provides preclinical data suggesting etanercept-mediated modulation of inflammation as a promising approach to reduce WMI caused by sepsis or necrotizing enterocolitis in preterm infants.http://link.springer.com/article/10.1186/s12868-019-0529-1NewbornWhite matter injurySystemic inflammationTNF-α antagonist |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Seung Han Shin Ee-Kyung Kim Kyung-yup Lee Han-Suk Kim |
spellingShingle |
Seung Han Shin Ee-Kyung Kim Kyung-yup Lee Han-Suk Kim TNF-α antagonist attenuates systemic lipopolysaccharide-induced brain white matter injury in neonatal rats BMC Neuroscience Newborn White matter injury Systemic inflammation TNF-α antagonist |
author_facet |
Seung Han Shin Ee-Kyung Kim Kyung-yup Lee Han-Suk Kim |
author_sort |
Seung Han Shin |
title |
TNF-α antagonist attenuates systemic lipopolysaccharide-induced brain white matter injury in neonatal rats |
title_short |
TNF-α antagonist attenuates systemic lipopolysaccharide-induced brain white matter injury in neonatal rats |
title_full |
TNF-α antagonist attenuates systemic lipopolysaccharide-induced brain white matter injury in neonatal rats |
title_fullStr |
TNF-α antagonist attenuates systemic lipopolysaccharide-induced brain white matter injury in neonatal rats |
title_full_unstemmed |
TNF-α antagonist attenuates systemic lipopolysaccharide-induced brain white matter injury in neonatal rats |
title_sort |
tnf-α antagonist attenuates systemic lipopolysaccharide-induced brain white matter injury in neonatal rats |
publisher |
BMC |
series |
BMC Neuroscience |
issn |
1471-2202 |
publishDate |
2019-08-01 |
description |
Abstract Background Systemic inflammation is an important risk factor for neurodevelopmental impairments in preterm infants. Premyelinating oligodendrocytes are main building blocks of white matter in preterm infants and vulnerable to oxidative stress and excitotoxic stress. Tumour necrosis factor-α (TNF-α) plays important roles in systemic inflammation and local inflammation leading to apoptosis of premyelinating oligodendrocytes and white matter injury (WMI) in brain tissue. This study was conducted to investigate whether etanercept, a TNF-α antagonist, could attenuate systemic lipopolysaccharide (LPS)-induced WMI in the immature brain. Results We found that intraperitoneal LPS administration caused systemic and local inflammation in brain tissue. Subsequent etanercept treatment significantly attenuated LPS-induced inflammation in brain tissue as well as in systemic circulation. Intraperitoneal LPS also induced microgliosis and astrocytosis in the cingulum and etanercept treatment reduced LPS-induced microgliosis and astrocytosis. Additionally, systemic LPS-induced apoptosis of oligodendrocyte precursor cells was observed, which was lessened by etanercept treatment. The concentration of etanercept in the CSF was higher when it was administrated with LPS than when administrated with a vehicle. Conclusions It appears that etanercept reduce WMI in the neonatal rat brain via attenuation of systemic and local inflammation. This study provides preclinical data suggesting etanercept-mediated modulation of inflammation as a promising approach to reduce WMI caused by sepsis or necrotizing enterocolitis in preterm infants. |
topic |
Newborn White matter injury Systemic inflammation TNF-α antagonist |
url |
http://link.springer.com/article/10.1186/s12868-019-0529-1 |
work_keys_str_mv |
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