Intrauterine Subclinical Inflammation Sensitizes Hypoxic Ischemia- Induced Injury in the Immature Rat Brain and the Mechanisms

Objective: To investigate whether intrauterine subclinical infection sensitizes HI-induced brain injury in the immature rat, the changes and significance of Histone deacetylases (HDACs) in brain injury, and the effects of erythropoietin on White Matter injury. Methods: Pregnant SD rats at gestation day 15 were injected LPS (0.3 mg/kg) or sterile saline (N.S) intraperitoneally, continue to rise until delivery. Rat pups on postnatal (P) days 5 were randomly assigned into 4 groups: control group, LPS, HI, LPS+HI group. Intervention groups included LPS+HI+N.S group and LPS+HI+EPO group. Brain tissues were observed on the time point of 6 h, 24 h and 7d after 40-minHI. The expression of TNF-α and HDACs in the brain homogenate were measured by ELISA. The level of MBP and MAP-2 were detected by immunohistochemistry staining. The expression of MAP-2 mRNA and HDAC1 mRNA were detected by real time PCR. Results: The expression of TNF-a, HDACs and HDAC1 mRNA from high to low were LPS+HI, LPS/HI, control group, but MBP was the lowest, there were significant differences between LPS+HI group and the other three groups (P 0.05). The expression of MBP in LPS+HI+EPO was higher than LPS+HI+N.S, the difference was statistically significant (P<0.05). There exist necrosis areas in the cortex of LPS+HI group in MAP-2 immunohistochemistry staining, but not in other three groups. Compared with the other three groups, the expression of MAP-2 mRNA in LPS +HI group decreased 6h after HI, and gradually rise, the differences were statistically significant. Conclusions: Intrauterine subclinical inflammation sensitizes HI-Induced injury in the immature rat brain, and lead to epigenetic changes. EPO plays a protective role to white matter after brain damage.