Placental-derived mediators drive neural injury in CHORIO. Sham or CHORIO placental explants were cultured on inserts and placental conditioned media (PCM) assayed for toxic mediators and inflammatory drivers (A-B). CHORIO placentas secrete more IL-1β (A), and TNF-α (B) compared to sham placentas. To determine the effect of CHORIO PCM on the developing brain, PCM from naive or CHORIO placental explants was cultured with postnatal day 2 (P2) brain slices (C). PCM from CHORIO placental explants induced high levels of CXCL1 in P2 brain slices. (n = 4–5, two independent experiments, *p < 0.05, **p < 0.01, ***p < 0.001).