LAUSR

Hyperoxia exposure can cause dramatic release of proinflammatory cytokines, leading to neuronal apoptosis and inducing white matter damage in newborn mouse brains. Some studies indicated that the Notch activation was provoked during inflammation and might regulate adaptive and innate immune responses. Moreover, the pathway also regulated oligodendrocyte maturation which was disrupted in neonatal mice after hyperoxia exposure. This study sought to investigate whether the Notch signalling activation contributed to immature brain damage after hyperoxia exposure. Cellular changes in the white matter (WM) of neonatal wild-type mice exposed to 80% oxygen from postnatal day 3 (P3) to day 5 (P5) were determined. Moreover, in order to further confirm the relationship between the Notch signalling pathway and hyperoxia-induced periventricular white matter injury, mice were pre-treated with a γ-secretase inhibitor (N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester, DAPT), which inhibits activation of the Notch pathway before exposure to hyperoxia. The results suggested that expression of myelin basic protein (MBP) increased in P12 mice subjected to hyperoxia after DAPT pretreatment. Moreover, hyperoxia could cause mature oligodendrocytes (MBP+) counts decreased with an obvious inverse increase in OPCs (NG2+) after hyperoxia on P12, DAPT pretreatment significantly ameliorated disruption of oligodendrocytes maturation induced by hyperoxia. Our results also demonstrated that DAPT could reduce memory impairment induced by hyperoxia exposure. Taken together, these results suggest that hyperoxia exposure induces both brain damage in the developing brain and behavioural abnormalities through the Notch signalling activation. And modulation of γ-secretase, selectively interfering with the Notch signalling pathway, could improve adverse outcomes induced by hyperoxia.