Abstract
Little is known about roles of inflammation and hypoxic ischemia (HI) in the generation of neuroinflammation and damage of blood-brain barrier (BBB) in the white matter (WM) that displays regional vulnerability in preterm infants. We investigated whether low-dose lipopolysaccharide (LPS) sensitizes HI-induced WM injury in postpartum (P) day 2 rat pups by selectively increasing neuroinflammation and BBB damage in the WM. Pups received LPS (0.05 mg/kg) (LPS + HI) or normal saline (NS + HI) followed by 90-min HI. LPS and NS group were the pups that had LPS or NS only. Myelin basic protein immunohistochemistry on P11 showed WM injury in LPS + HI group, but not in NS + HI, LPS, and NS groups. In contrast, no gray matter injury was found in the four groups. LPS + HI group also showed decreased number of oligodendrocytes in the WM 72-h postinsult. In the same brain region, increases of activated microglia, TNF-α expression, BBB leakage, and cleaved caspase-3 positive cells were much more prominent in LPS + HI group than in the other three groups 24-h postinsult. The oligodendrocytes were the major cells with cleaved caspase-3 expression. We concluded that low-dose LPS sensitized HI-induced WM injury in the immature brain by selectively up-regulating neuroinflammation and BBB damage in the WM.
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Abbreviations
- BBB:
-
blood-brain barrier
- HI:
-
hypoxic ischemia
- IOD:
-
integrated optical density
- LPS:
-
lipopolysaccharide
- MBP:
-
myelin basic protein
- NS:
-
normal saline
- VLBW:
-
very-low-birth-weight
- WM:
-
white matter
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Acknowledgements
We thank Chien-Jung Ho for her skillful technical assistance with animal preparations.
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Supported by grants from the Taiwan National Health Research Institute (NHRI-EX 97-9414NI), the National Science Counsel (NSC: 97-2811-B-006-014), Chi Mei Medical Center (CMNCKU 9802), and the Center for Gene Regulation and Signal Transduction Research, National Cheng Kung University.
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Wang, LW., Chang, YC., Lin, CY. et al. Low-Dose Lipopolysaccharide Selectively Sensitizes Hypoxic Ischemia-Induced White Matter Injury in the Immature Brain. Pediatr Res 68, 41–47 (2010). https://doi.org/10.1203/PDR.0b013e3181df5f6b
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DOI: https://doi.org/10.1203/PDR.0b013e3181df5f6b
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