Intrauterine Subclinical Inflammation Sensitizes Hypoxic Ischemia- Induced Injury in the Immature Rat Brain and the Mechanisms
|Xu Fa-lin1,2*, Zhang Yan-hua1,2 and Guo Jia-jia1,2|
|1Department of Pediatrics, the Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China|
|2Henan Provincial Key Laboratory of Neonatal Brain Injury, Zhengzhou 450052, China|
|Corresponding Author :||Xu Fa-lin
Department of Pediatrics
Third Affiliated Hospital of Zhengzhou University
Zhengzhou 450052, P.R China
E-mail: [email protected]
|Received Janaury 09, 2014; Accepted February 04, 2014; Published February 06, 2014|
|Citation: Fa-lin X, Yan-hua Z, Jia-jia G (2014) Intrauterine Subclinical Inflammation Sensitizes Hypoxic Ischemia-Induced Injury in the Immature Rat Brain and the Mechanisms. J Neonatal Biol 3:126. doi:10.4172/2167-0889.1000126|
|Copyright: © 2014 Fa-lin X, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.|
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), there were no difference between 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.