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Background  Several clinical conditions are associated with white matter injury, including periventricular white matter injury (PWMI), which is a form of brain injury sustained by preterm infants. It has been suggested that white matter injury in this condition is due to altered oligodendrocyte (OL) development or death, resulting in OL loss and hypomyelination. At present drugs are not available that stimulate OL proliferation and promote myelination. Evidence suggests that depolarizing stimuli reduces OL proliferation and differentiation, whereas agents that hyperpolarize OLs stimulate OL proliferation and differentiation. Considering that the drug diazoxide activates K ATP  channels to hyperpolarize cells, we tested if this compound could influence OL proliferation and myelination.    Methodology/Findings  Studies were performed using rat oligodendrocyte precursor cell (OPC) cultures, cerebellar slice cultures, and an  in vivo  model of PWMI in which newborn mice were exposed to chronic sublethal hypoxia (10% O 2 ). We found that K ATP  channel components Kir 6.1 and 6.2 and SUR2 were expressed in oligodendrocytes. Additionally, diazoxide potently stimulated OPC proliferation, as did other K ATP  activators. Diazoxide also stimulated myelination in cerebellar slice cultures. We also found that diazoxide prevented hypomyelination and ventriculomegaly following chronic sublethal hypoxia.    Conclusions  These results identify KATP channel components in OLs and show that diazoxide can stimulate OL proliferation  in vitro . Importantly we find that diazoxide can promote myelination  in vivo  and prevent hypoxia-induced PWMI.

Diazoxide Promotes Oligodendrocyte Precursor Cell Proliferation and Myelination