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Updated: Jan 20, 2026
Laser-Induced Brain Injury in the Motor Cortex of Rats
Published on: September 26, 2020
TNF-α antagonist attenuates systemic lipopolysaccharide-induced brain white matter injury in neonatal rats
Seung Han Shin1, Ee-Kyung Kim2, Kyung-Yup Lee1
1Department of Pediatrics, Seoul National University College of Medicine, Seoul National University Children's Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-769, South Korea.
Insights
Etanercept, a TNF-α antagonist, reduced white matter injury in neonatal rat brains by decreasing inflammation. This suggests etanercept may protect preterm infants from brain damage caused by sepsis.
Area of Science:
- Neuroscience
- Immunology
- Developmental Biology
Background:
- Systemic inflammation is a key risk factor for neurodevelopmental impairments in preterm infants.
- Premyelinating oligodendrocytes are vulnerable to oxidative and excitotoxic stress, leading to white matter injury (WMI).
- Tumour necrosis factor-alpha (TNF-α) contributes to inflammation, oligodendrocyte apoptosis, and WMI.
Purpose of the Study:
- To investigate if etanercept, a TNF-α antagonist, can reduce lipopolysaccharide (LPS)-induced WMI in immature brains.
- To evaluate etanercept's effect on inflammation and oligodendrocyte precursor cell apoptosis.
Main Methods:
- Administered intraperitoneal LPS to induce systemic and local brain inflammation in neonatal rats.
- Treated rats with etanercept to assess its anti-inflammatory and neuroprotective effects.
- Measured etanercept concentration in cerebrospinal fluid (CSF).
Main Results:
- LPS induced significant inflammation in brain tissue and systemic circulation.
- Etanercept treatment attenuated LPS-induced inflammation and reduced microgliosis and astrocytosis.
- Etanercept lessened LPS-induced apoptosis of oligodendrocyte precursor cells and showed higher CSF concentrations when co-administered with LPS.
Conclusions:
- Etanercept reduces WMI in neonatal rat brains by mitigating systemic and local inflammation.
- Preclinical data suggest etanercept is a promising therapeutic for WMI in preterm infants due to sepsis or necrotizing enterocolitis.
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.
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