Knockdown of endogenous GR exacerbates mild HI injury in the male neonatal rat pup brain. GR siRNA (100 pmol) or negative control (100 pmol) was injected by ICV injection 48 h on postnatal day 7 (P7) before HI-injury. HI-injury was performed on postnatal day 9 (P9) for 60 min in 8% FiO2. We separated sex into the following groups: negative control (negative control: male, n = 5; female, n = 8) versus GR siRNA (male, n = 5; female, n = 11). In the male population, GR siRNA increased infarct volume. No significant difference was seen in the female population, although the total brain injury was increased with a mild hypoxic-ischemic model. Data are means ± SEM, * p = 0.0315, GR siRNA vs. negative control.