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.
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.
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.