Abstract
Background: Epidemiological and experimental studies show that hyperoxia and infection are independently associated with injury to the developing brain. Moreover inflammation may precondition the fetal brain resulting in increased or decreased injury when exposed to a postnatal insult. We examined the combined effects of antenatal bacterial endotoxin and postnatal variable hyperoxia on the immature rat brain.
Methods: Pregnant rats were injected intraperitoneally on E18 and E19 with lipopolysaccharide (225mcg/kg) or saline. Dams and their pups were reared in room air or fluctuating hyperoxia (circa 10kPa). Pup brains were examined at P7 for myelin basic protein (MBP) in the internal and external capsules using immunohistochemistry. Quantification of MBP mRNA was also undertaken.
Results: In the group exposed to antenatal lipopolysaccharide alone immunohistochemistry showed a decrease in MBP at P7 but there was a marked increase in MBP mRNA expression. Pups exposed to both antenatal lipopolysaccharide and postnatal variable hyperoxia showed a further decrease in MBP (immunohistochemistry). MBP mRNA expression was also markedly suppressed. Postnatal variable hyperoxia had little effect on myelination at P7 (immunohistochemistry) but MBP mRNA was decreased.
Conclusion: These results show that antenatal inflammation reduces myelination in the motor tracts of the developing brain. The increase in MBP mRNA production suggests that hypomyelination induced by endotoxin may be transient and potentially reversible. Postnatal variable hyperoxia has a synergistic effect in depressing myelination further and this prolonged insult results in suppression of mRNA expression. Where preterm infants are exposed to antenatal inflammation, hyperoxia may continue to disrupt myelination postnatally.
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Pilley, E., Wade, J., Gillespie, T. et al. 33 Postnatal Variable Hyperoxia Suppresses Myelin Basic Protein Mrna Expression Induced by Antenatal Lipopolysaccharide. Pediatr Res 68 (Suppl 1), 20 (2010). https://doi.org/10.1203/00006450-201011001-00033
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DOI: https://doi.org/10.1203/00006450-201011001-00033