Low-dose lipopolysaccharide selectively sensitizes hypoxic ischemia-induced white matter injury in the immature brain

Lan Wan Wang, Ying Chao Chang, Chang Yi Lin, Jau Shyong Hong, Chao Ching Huang

Research output: Contribution to journalArticle

43 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)41-47
Number of pages7
JournalPediatric Research
Volume68
Issue number1
DOIs
Publication statusPublished - Jul 2010
Externally publishedYes

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Lipopolysaccharides
Ischemia
Wounds and Injuries
Brain
Blood-Brain Barrier
Oligodendroglia
Caspase 3
White Matter
Myelin Basic Protein
Microglia
Premature Infants
Postpartum Period
Immunohistochemistry
Inflammation

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Low-dose lipopolysaccharide selectively sensitizes hypoxic ischemia-induced white matter injury in the immature brain. / Wang, Lan Wan; Chang, Ying Chao; Lin, Chang Yi; Hong, Jau Shyong; Huang, Chao Ching.

In: Pediatric Research, Vol. 68, No. 1, 07.2010, p. 41-47.

Research output: Contribution to journalArticle

Wang, Lan Wan ; Chang, Ying Chao ; Lin, Chang Yi ; Hong, Jau Shyong ; Huang, Chao Ching. / Low-dose lipopolysaccharide selectively sensitizes hypoxic ischemia-induced white matter injury in the immature brain. In: Pediatric Research. 2010 ; Vol. 68, No. 1. pp. 41-47.
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