Effects of progesterone on hippocampal ultrastructure and expression of inflammatory mediators in neonatal rats with hypoxic-ischemic brain injury

Progesterone (PROG) has been shown to exhibit a protective function against hypoxic-ischemic brain damage. The aim of the present study was to study the effects of PROG in a neonatal rat model of hypoxic-ischemic brain injury. A total of 30 Wistar rats, aged 7 days, were randomly divided into three groups: Sham, model and PROG. The rats in the model and PROG groups underwent a left common carotid artery ligation and were placed in a sealed container at 37°C with 8% O(2) and 92% N(2) gas mixtures for 2.5 h to establish animal models of hypoxic-ischemic encephalopathy. The rats in the PROG group were intraperitoneally treated with 8 mg/kg PROG solution 30 min prior to the induction of hypoxia-ischemia. All animals were sacrificed after 24 h and neuronal changes were observed with electron microscopy to investigate the hypoxic-ischemic brain damage. The protein and mRNA expression levels of tumor necrosis factor-α (TNF-α) and nuclear factor-κB (NF-κB) in the hippocampus were detected by immunohistochemistry and quantitative polymerase chain reaction, respectively. The results revealed that the neuronal structures in the sham group were normal. The neuronal structures in the model group exhibited cavitation changes, but these were reduced following PROG administration. The protein and mRNA expression levels of TNF-α and NF-κB in the hippocampal neurons were increased in the model group, and pretreatment with 8 mg/kg PROG was shown to reduce the expression levels of these inflammatory mediators. Therefore, PROG was shown to exert an important protective function in hypoxic-ischemic brain injury by inhibiting the cascade of inflammatory injury induced by TNF-α and NF-κB.