Abstract
To examine the possible role of inflammatory cytokines in mediating neonatal brain injury, we investigated effects of intra-cerebral injection of IL-1beta (IL-1β) or tumor necrosis factor-alpha (TNFα) on brain injury in the neonatal rat. A stereotaxic intracerebral injection of IL-1βor TNFα(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-1βor TNFα. IL-1βinduced 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-1βalso significantly reduced the number of developing oligodendrocytes (OLs) 24 h after the injection and this impairment was not prevented by NBQX. On the contrary, TNFα 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-1βtreated rat brain. MBP expression in the TNFα treated rat brain was less affected. The overall results indicate that IL-1β may directly cause injuries to developing OLs and impair myelination in the neonatal rat brain and TNFα may have different roles in mediating brain injury.
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Abbreviations
- IL-1β:
-
interleukin-1beta
- TNFα:
-
tumor necrosis factor-alpha
- PVL:
-
periventricular leukomalacia
- LPS:
-
lipopolysaccharide
- HI:
-
hypoxiaischemia
- OL:
-
oligodendrocyte
- NF:
-
neurofilament
- GFAP:
-
glial fibrillary acidic protein
- MBP:
-
myelin basic protein
- NBQX:
-
6-nitro-7-sulfamoylbenzoquinoxaline-2,3-dione
- PN:
-
polymorphonuclear
- TUNEL:
-
terminal deoxynucleotidyl transferase-mediated uridine 5′-triphosphate-biotin nick end labeling
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This work was supported by HD 35496.
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Cai, Z., Lin, S., Pang, Y. et al. Brain Injury Induced by Intracerebral Injection of Interleukin-1beta and Tumor Necrosis Factor-alpha in the Neonatal Rat. Pediatr Res 56, 377–384 (2004). https://doi.org/10.1203/01.PDR.0000134249.92944.14
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DOI: https://doi.org/10.1203/01.PDR.0000134249.92944.14
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