In the present study, we observed that inhibition of L-PGDS by SeCl4 abrogated dexamethasone pretreatment induced neuroprotective effects in neonatal rat brains with HI insult, which not only confirmed its protective role in various brain injuries but also indicated its key role in glucocorticoids-GR signaling mediated neuroprotection. Here, NR3C1 is linked to brain injury.