Intraventricular hemorrhage (IVH) remains a major cause of white matter injury 
in preterm infants with no viable therapeutic strategy to restore myelination. 
Maturation of oligodendrocytes and myelination is influenced by thyroid hormone 
(TH) signaling, which is mediated by TH receptor α (TRα) and TRβ. In the brain, 
cellular levels of TH are regulated by deiodinases, with deiodinase-2 mediating 
TH activation and deiodinase-3 TH inactivation. Therefore, we hypothesized that 
IVH would decrease TH signaling via changes in the expression of deiodinases 
and/or TRs, and normalization of TH signaling would enhance maturation of 
oligodendrocytes and myelination in preterm infants with IVH. These hypotheses 
were tested using both autopsy materials from human preterm infants and a rabbit 
model of IVH. We found that deiodinase-2 levels were reduced, whereas 
deiodinase-3 levels were increased in brain samples of both humans and rabbits 
with IVH compared with controls without IVH. TRα expression was also increased 
in human infants with IVH. Importantly, treatment with TH accelerated the 
proliferation and maturation of oligodendrocytes, increased transcription of 
Olig2 and Sox10 genes, augmented myelination, and restored neurological function 
in pups with IVH. Consistent with these findings, the density of myelinating 
oligodendrocytes was almost doubled in TH-treated human preterm infants compared 
with controls. Thus, in infants with IVH the combined elevation in deiodinase-3 
and reduction in deiodinase-2 decreases TH signaling that can be worsened by an 
increase in unliganded TRα. Given that TH promotes neurological recovery in IVH, 
TH treatment might improve the neurodevelopmental outcome of preterm infants 
with IVH.