Brain injury induced by intracerebral injection of interleukin-1beta and tumor necrosis factor-alpha in the neonatal rat
Abstract
To examine the possible role of inflammatory cytokines in mediating neonatal brain injury, we investigated effects of intracerebral injection of IL-1beta (IL-1beta) or tumor necrosis factor-alpha (TNFalpha) on brain injury in the neonatal rat. A stereotaxic intracerebral injection of IL-1beta or TNFalpha (10 ng per pup) was performed in postnatal day 5 (P5) SD rats. Although no necrosis of neurons was found, increased astrogliosis, as indicated by GFAP positive staining was observed 24 and 72 h following the injection of IL-1beta or TNFalpha. IL-1beta induced apoptotic cell death in the rat brain 24 h after the injection, as indicated by increases in positive TUNEL staining and caspase-3 activity, and apoptotic cell death was partially blocked by systemic administration of NBQX, an antagonist of the AMPA glutamate receptor. IL-1beta also significantly reduced the number of developing oligodendrocytes (OLs) 24 h after the injection and this impairment was not prevented by NBQX. On the contrary, TNFalpha induced a much smaller increase in the number of TUNEL positive cells and did not reduce the number of developing OLs. By P8, myelin basic protein (MBP) was clearly detected in the control rat brain, while MBP positive staining was very weak, if any, in the IL-1beta treated rat brain. MBP expression in the TNFalpha treated rat brain was less affected. The overall results indicate that IL-1beta may directly cause injuries to developing OLs and impair myelination in the neonatal rat brain and TNFalpha may have different roles in mediating brain injury.
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Neonatal administration of inflammatory cytokines such as Il-1β reduces the number of developing oligodendrocytes.
“Neonatal administration of inflammatory cytokines such as Il-1β reduces the number of developing oligodendrocytes (Cai et al., 2004; Fan et al., 2009).”
From Redox dysregulation, neuroinflammation, and NMDA receptor hypofunction: A “central hub” in schizophrenia pathophysiology? (2016) · cites this paper as Cai et al., 2004
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- Authors
- Cai, Z., Lin, S., Pang, Y., & Rhodes, P. G.
- Affiliations
- University of Mississippi Medical Center (US)
- Corresponding author
- Cai, Zhengwei
- Venue
- Pediatric Research
- Published
- 2004-09
- Volume
- 56
- Issue
- 3
- Pages
- 377-384
- ISSN
- 0031-3998 (ISSN-L)
- 1530-0447
- OpenAlex
- W2004941059
- Cited by
- 111
- References
- 46
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 1 · 2023: 2 · 2022: 7 · 2021: 4 · 2020: 9 · 2019: 8 · 2018: 6 · 2017: 7 · 2016: 4 · 2015: 3 · 2014: 3 · 2013: 6 · 2012: 7
- FWCI
- 2.65
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Pediatric 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
- Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Keywords
- neonatal brain injury, IL-1β, TNF-α, inflammatory cytokines, astrocyte activation, glial fibrillary acidic protein, neuronal apoptosis, caspase-3, NBQX, oligodendrocyte development, myelination, myelin basic protein, intracerebral injection, postnatal rat brain
- MeSH terms
- Animals, Animals, Newborn, Brain Injuries, Cerebral Cortex, Myelin Basic Protein, Humans, Infant, Inflammation, Interleukin-1, Oligodendroglia, Quinoxalines, Tumor Necrosis Factor-alpha, Rats, Sprague-Dawley, Apoptosis, Receptors, AMPA, Excitatory Amino Acid Antagonists, Caspases, In Situ Nick-End Labeling, Rats, Caspase 3
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