Progesterone reduces inflammation and apoptosis in neonatal rats with hypoxic ischemic brain damage through the PI3K/Akt pathway.

A neonatal rat model with hypoxic ischemic brain damage (HIBD) was established. Forty 7-day-old neonatal Wistar rats were randomly divided into four groups: sham operation, model, progesterone and Akt inhibitor. Electron microscopy revealed that the neonatal rats with HIBD showed neuronal changes. The protein expression levels of pAkt, Nuclear factor κB (NF-κB) and Bcl-2 in the hippocampus were detected by immunohistochemistry and Western blot. The neuronal structure was normal in the sham operation group after HIBD for 24 h. Cavitation change due to hypoxic ischemic brain damage was observed in the neurons of the model group. Progesterone treatment improved neuronal damage and cavitation. Neuronal cavitation was clearly changed in the Akt inhibitor group. The protein expression levels of hippocampal pAkt and Bcl-2 did not significantly change after HIBD, whereas that of NF-κB increased. Progesterone pre-treatment increased the expression levels of pAkt and Bcl-2 but decreased that of NF-κB. The protein expression levels of pAkt and Bcl-2 decreased in the Akt inhibitor group, whereas that of NF-κB increased. This result indicates that progesterone can decrease inflammation in HIBD, inhibit apoptosis and protect the brain by activating the Phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signalling pathway.