PS-117aHyperoxia Reduces Astroglial Pdgf Expression And Impairs Oligodendroglial Development In The Cerebellum

Although brain injury of preterm infants has widely been ascribed to the cerebrum, recent studies demonstrate that injury of the cerebellum often occurs, too. However, mechanisms of the cerebellar injury are hardly understood. In general, hypoxia-ischemia, infection/inflammation, and hyperoxia are supposed to be toxic stimuli in the immature brain.We used a hyperoxia model established in rats by using 80% O2 exposure for 24 h from P6 to P7, and determined development and maturation of oligodendroglial cells in the cerebellum during recovery in room air until P30. Expression of platelet derived growth factor (PDGF)-A as a crucial factor for oligodendroglial development was determined in cerebellar tissue and in cultures of cerebellar astroglia.Volume of the cerebellum measured by MRI was significantly reduced in P30 rats after hyperoxia as compared to control litters (208 vs. 232 mu L respectively, p < 0.05). Myelination measured by MBP in immunostainings and Western blots was significantly reduced during recovery from P9 to P30. Numbers of NG2+TUNEL+ oligodendroglial precursor cells were increased by hyperoxia, and oligodendroglial maturation towards CC1+ stages was significantly diminished. Expression of PDGF-A was reduced after hyperoxia by 46% at P7 and by 27% at P30 (n = 4; p < 0.01 each). In astrocyte cultures, exposure to 80% O2 also caused a significant downregulation of PDGF-A expression by 42% (n = 6; p < 0.01).Hyperoxia resembles critical features of the cerebellar pathology found in preterm infants. Astroglial changes caused by hyperoxia include reduced PDGF synthesis and are likely to contribute to oligodendroglial damage in the cerebellum.