Background
Hypoxic-ischemic injury (HI) to preterm brain
Conclusion
Changes in specific mature miRs expressed in OPCs following HI may contribute to white matter injury.
Methods
We inducibly deleted the miR-processing enzyme Dicer in OPCs using a tamoxifen-inducible NG2CreER(T2) transgene in Dicer(fl/fl) mice. After HI, mice were analyzed for OPC differentiation using immunofluorescence and for white matter formation by Luxol fast blue (LFB) staining. Functional recovery from injury was investigated using digital gait analysis. We also tested whether HI changed miRs known to regulate OPC differentiation using quantitative RT-PCR.
Results
Perinatal HI induced significant increases in miR-138 and miR-338, two miRs known to regulate OPC differentiation. Knockdown of Dicer increased myelin basic protein and LFB staining within the corpus callosum after HI. In addition, there was significant improvement in motor function 14 and 24 d post lesion.