Perinatal inflammation results in decreased oligodendrocyte numbers in adulthood

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• 作者：Am ; a E. Graf ; Krista M. Haines ; Christopher R. Pierson ; Brad N. Bolon ; Ronald H. Houston ; Markus Velten ; Kathryn M. Heyob ; Lynette K. Rogers
• 关键词：Lipopolysaccharide ; Inflammation ; Hyperoxia ; Oligodendrocyte ; Microglia ; White matter injury ; Premature brain injury ; Development ; Periventricular leukomalacia
• 刊名：Life Sciences
• 出版年：17 January, 2014
• 年：2014
• 卷：94
• 期：2
• 页码：164-171
• 全文大小：2212 K

文摘

Aims

Maternal inflammation is a risk factor for preterm birth, and premature infants are often exposed to supplemental oxygen as a life-sustaining therapy. While more immature neonates are surviving, rates of neurodevelopmental impairment are not improving. We developed a novel mouse model with clinically relevant exposures to test the hypothesis that systemic maternal inflammation with transient neonatal hyperoxia exposure will induce a phenotype similar to diffuse periventricular leukomalacia (PVL) like that observed in premature human infants.

Main methods

Timed-pregnant C3H/HeN mice received intraperitoneal injections of lipopolysaccharide (LPS) or saline on embryonic day 16. Newborn pups were placed in room air (RA) or 85% oxygen (O₂) for 14 days, followed by 14 days in RA recovery. Oligodendroglial and microglial populations were evaluated at 14 and 28 days.

Key findings

Brain weight to body weight ratios were lower in mice exposed to LPS. Oligodendrocyte numbers were decreased significantly in the cerebral cortex and hippocampus in groups exposed to LPS or LPS/O₂ at 14 days, and persisted in the cerebral cortex at 28 days for LPS/O₂ mice. At day 14, cleaved caspase 3 was increased and numbers of microglia were elevated in the cerebral cortex and hippocampus of LPS/O₂ animals.

Significance

These data indicate that combining systemic maternal LPS and neonatal hyperoxic exposure impairs myelination, and suggests that this novel mouse model may represent a subtle, diffuse form of periventricular white matter injury that could provide a clinically relevant platform for further study of perinatal brain injury.