Low-dose lipopolysaccharide selectively sensitizes hypoxic ischemia-induced white matter injury in the immature brain.
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-alpha 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.
Wang
Lan-Wan
LW
Institutes of Clinical Medicine, National Cheng Kung University College of Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Kaohsiung 833, Taiwan.
Chang
Ying-Chao
YC
Lin
Chang-Yi
CY
Hong
Jau-Shyong
JS
Huang
Chao-Ching
CC
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism / Q000473:pathology; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000473:pathology; D009836:Oligodendroglia / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D011247:Pregnancy; D047928:Premature Birth; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
D008070:Lipopolysaccharides