Differential roles of tumor necrosis factor-α and interleukin-1 β in lipopolysaccharide-induced brain injury in the neonatal rat
Abstract
Increasing data provide support for the hypothesis that inflammatory cytokines mediate inflammation-induced injury to developing white matter. In the present study, roles of tumor necrosis factor-alpha (TNFalpha) and interleukin-1 beta (IL-1beta) in mediating lipopolysaccharide (LPS)-induced brain injury were investigated by co-administration of LPS with IL-1 receptor antagonist (IL-1ra) or TNFalpha antibody in the 5-day-old rat brain. Intracerebral injection of LPS and other agents was performed in a stereotaxic apparatus at the location of 1.0 mm posterior and 1.0 mm lateral to the bregma, and 2.0 mm deep to the skull surface at the left hemisphere. Brain injury was examined in brain sections 3 and 11 days after LPS injection. LPS-induced inflammatory responses were evidenced by great increases in TNFalpha and IL-1beta concentrations in the neonatal rat brain 6 h after LPS injection. White matter rarefaction was observed in 71% (five out of seven) of the rat brains 3 days after LPS injection and bilateral ventricle dilation was found in 71% (five out of seven) of the P8 rat brains and in 100% of the P16 rat brains (four out of four). These alterations were not found in the control rat brains. No apparent histological changes in gray matter were observed in the LPS-injected rat brains. LPS injection also resulted in injuries to oligodendrocytes (OLs) and hypomyelination, as indicated by reduced immunostaining for O4 and myelin basic protein (MBP). Increased astrogliosis, as…
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These same compounds have also been implicated in the neural tissue damage induced by injection of LPS in rodent brain.
“These same compounds have also been implicated in the neural tissue damage induced by injection of LPS in rodent brain (Iravani et al., 2002;Cai et al., 2003;Arai et al., 2004;Qin et al., 2004).”
From Neurotoxic Activation of Microglia Is Promoted by a Nox1-Dependent NADPH Oxidase (2008) · cites this paper as Cai et al., 2003
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TNFα promotes proliferation of oligodendrocyte progenitors and remyelination
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Microglia in the developing brain: a potential target with lifetime effects
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“For example, perinatal endotoxin administration induces cytokine expression, apoptosis, and glial activation in the immature rat brain, factors that have been linked to white matter injury (Cai et al., 2003; Golan et al., 2005).”
Neurotoxic Activation of Microglia Is Promoted by a Nox1-Dependent NADPH Oxidase
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Pathophysiology of glia in perinatal white matter injury
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Self-citationWang, K.-C., Fan, L.-W., Kaizaki, A., Pang, Y., Cai, Z., & Tien, L.-T. (2013) · Neuroscience · doi:10.1016/j.neuroscience.2012.12.049 · Cited by 92 · see citing works
Self-citationFan, L., Mitchell, H. J., Tien, L., Zheng, B., Pang, Y., Rhodes, P. G., & Cai, Z. (2008) · Developmental Neurobiology · doi:10.1002/dneu.20591 · Cited by 29 · see citing works
Self-citationFan, L.-W., Mitchell, H. J., Tien, L.-T., Rhodes, P. G., & Cai, Z. (2009) · Experimental Neurology · doi:10.1016/j.expneurol.2009.08.003 · Cited by 26 · see citing works
Self-citation
- Authors
- Cai, Z., Pang, Y., Lin, S., & Rhodes, P. G.
- Affiliations
- University of Mississippi Medical Center (US)
- Corresponding author
- Cai, Zhengwei
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 2003-06
- Volume
- 975
- Issue
- 1-2
- Pages
- 37-47
- ISSN
- 0006-8993 (ISSN-L)
- OpenAlex
- W1993376226
- Cited by
- 173
- References
- 2
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2022: 3 · 2021: 4 · 2020: 3 · 2019: 2 · 2018: 6 · 2017: 9 · 2016: 4 · 2015: 13 · 2014: 4 · 2013: 11 · 2012: 17
- FWCI
- 10.42
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD35496)
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Neonatal and fetal brain pathology
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- TNF-α, IL-1β, lipopolysaccharide, neonatal brain injury, white matter injury, interleukin-1 receptor antagonist, TNF-alpha antibodies, oligodendrocyte damage, hypomyelination, astrocyte activation, caspase-3, neuroinflammation, neuroprotection
- MeSH terms
- Animals, Animals, Newborn, Astrocytes, Encephalitis, Myelin Basic Protein, Female, Glial Fibrillary Acidic Protein, Immunohistochemistry, Injections, Intraventricular, Interleukin-1, Lipopolysaccharides, Male, Myelin Sheath, Oligodendroglia, Stereotaxic Techniques, Tumor Necrosis Factor-alpha, Rats, Sprague-Dawley, Caspases, Rats, Caspase 3
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