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TNF-α antagonist attenuates systemic lipopolysaccharide-induced brain white matter injury in neonatal rats

Cited 4 time in Web of Science Cited 5 time in Scopus
Authors
Shin, Seung Han; Kim, Ee-Kyung; Lee, Kyung-yup; Kim, Han-Suk
Issue Date
2019-08-30
Publisher
BioMed Central
Citation
BMC Neuroscience, 20(1):45
Keywords
NewbornWhite matter injurySystemic infammationTNF-α antagonist
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.
ISSN
1471-2202
Language
English
URI
https://hdl.handle.net/10371/162629
DOI
https://doi.org/10.1186/s12868-019-0529-1
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College of Medicine/School of Medicine (의과대학/대학원)Pediatrics (소아과학전공)Journal Papers (저널논문_소아과학전공)
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