Presented at the Neonatal Society 2010 Autumn Meeting.
Pilley E, Wade J, Gillespie T, Laing IA, Becher JC
Jennifer Brown Research Laboratory, Centre for Reproductive Biology, QMRI, University of Edinburgh
Background: Epidemiological and experimental studies show that hyperoxia and infection are independently associated with injury to the developing brain (1-3). Moreover inflammation may precondition the fetal brain resulting in increased or decreased injury when exposed to subsequent hypoxia-ischaemia (4). We examined the combined effects of antenatal bacterial endotoxin and postnatal variable hyperoxia on the developing rodent white matter.
Methods: Pregnant rats received intraperitoneal lipopolysaccharide (225mcg/kg) or saline on E18 and E19. Dams and their pups were then reared in room air or fluctuating hyperoxia (circa 10kPa) for seven days. Pup brains were examined at P7 for myelin basic protein (MBP) and glial fibrillary acidic protein (GFAP), a marker of astrogliosis, in the internal and external capsules using immunohistochemistry. Quantification of both MBP and GFAP mRNA was also undertaken.
Results: Pups exposed to antenatal LPS alone showed a significant decrease in MBP at P7 (p<0.001) but there was an increase in MBP mRNA expression. This increase in MBP mRNA was suppressed where pups who had been exposed to antenatal LPS were then reared in variable hyperoxia. LPS caused a significant increase in GFAP mRNA expression (p<0.001), which was further increased where pups were reared in variable hyperoxia (p<0.05). Postnatal variable hyperoxia had little effect on myelination at P7 (immunohistochemistry) but MBP mRNA was decreased (P<0.05).
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. Subsequent postnatal variable hyperoxia results in suppression of MBP mRNA expression and increases GFAP mRNA production. Where preterm infants are exposed to antenatal inflammation, hyperoxia may continue to disrupt myelination postnatally.
Corresponding author: firstname.lastname@example.org
1. Wu Ment Retard Dev Disabil Res Rev 2002
2. Cai et al Pediatr Res 2000
3. Felderhoff-Mueser et al Neurobiol Dis 2004
4. Eklind et al Eur J Neurosci 2001