Whether GPR17 has the same distribution and repair mechanism in immature white matter with periventricular leukomalacia (PVL) as in the adult brain remains to be determined. This study tried to explore the expression phase and site of GPR17, and to investigate the effect of silencing GPR17 on endogenous repair mechanism of immature white matter with PVL. Ischemic PVL in vivo results showed that GPR17 gene and protein expression increased more in the PVL than in the sham group at 12 h–24 h and 72h to 7 days after PVL. NG2+/GPR17+progenitor cells at 48 h–96 h and O4+/GPR17+precursor cells at 72h to 7d were also significantly increased in the PVL compared to the sham groups. Results in vitro showed that oxygen–glucose deprivation (OGD) also induced more GPR17 gene and protein expression than control at 48 h–72 h. There were more NG2+/GPR17+progenitor cells at 24 h–48 h and O4+/GPR17+precursor cells at 48 h–72 h in the OGD groups, as well. The functional role of GPR17 in the intrinsic repair response to ischemia was tested using GPR17 gene silencing. The progenitor cells and OL precursors in the OGD+GPR17 silencing group were both significantly less than those in the control, OGD and OGD+gene silencing control groups. The apoptotic percentage of cells in OGD+GPR17 silencing group was also much higher. In summary, ischemia-induced GPR17 expression was shown to contribute to glial-derived progenitor cell proliferation and differentiation into OL precursors, which may provide a therapeutic target for immature neonatal white matter injury after ischemia.
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