White matter damage after chronic subclinical inflammation in newborn mice.
Preterm infants exposed to inflammation are at increased risk of white matter injury and/or cerebral palsy. To investigate the effect of chronic inflammation on the developing white matter, we administered low-dose lipopolysaccharide once a day from postnatal days 3 to 11, examined white matter changes at postnatal day 12, and monitored serum levels of insulin-like growth factor 1 and insulin-like factor binding protein-3. A single injection of lipopolysaccharide decreased the serum insulin-like growth factor 1 level but not the insulin-like factor binding protein-3 level. At postnatal day 12, quantification of immunohistochemical staining for axonal, myelin, and oligodendrocyte markers revealed impaired myelination in subcortical white matter. In addition, brain gray matter volume decreased and spleen and liver weight increased at postnatal day 12. These data suggest chronic subclinical inflammation hampers development of white and gray matter in early life, which may be associated with insulin-like growth factor 1 deficiency.
Wang
Xiaoyang
X
Perinatal Center, Department of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, S-405 30 Gothenburg, Sweden. xiaoyang.wang@fysiologi.gu.se
Hellgren
Gunnel
G
Löfqvist
Chatarina
C
Li
Wenli
W
Hellström
Ann
A
Hagberg
Henrik
H
Mallard
Carina
C
D000818:Animals; D000831:Animals, Newborn; D001930:Brain Injuries / Q000209:etiology* / Q000473:pathology*; D002490:Central Nervous System / Q000473:pathology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007249:Inflammation / Q000139:chemically induced / Q000150:complications* / Q000473:pathology*; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008099:Liver / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D004676:Myelin Basic Protein / Q000378:metabolism; D016900:Neurofilament Proteins / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D011134:Polysaccharides / Q000009:adverse effects; D011247:Pregnancy; D013154:Spleen / Q000503:physiopathology
D018971:Insulin-Like Growth Factor Binding Protein 2; D015850:Interleukin-6; D008869:Microtubule-Associated Proteins; C079240:Mtap2 protein, mouse; D004676:Myelin Basic Protein; D016900:Neurofilament Proteins; D011134:Polysaccharides; D007334:Insulin-Like Growth Factor I