Changes in the PI3K/Akt/GSK-3β pathway at 24 h following HI brain damage in the neonatal rat brain tissue were observed, and a PI3K/Akt pathway inhibitor, wortmannin, was used to hinder HI brain damage in neonatal rats (wortmannin is a phosphatase inhibitor that prevents Akt phosphorylation and activity) to explore the neuroprotective effect mechanism of the PI3K/Akt/GSK-3β pathway in the process by which PROG attenuates HI brain injury. Here, GSK3B is linked to injury.