ANIMAL STUDY e-ISSN 1643-3750 © Med Sci Monit, 2016; 22: 5074-5081 DOI: 10.12659/MSM.898139
The Specific Protein Kinase R (PKR) Inhibitor C16 Protects Neonatal Hypoxia-Ischemia Brain Damages by Inhibiting Neuroinflammation in a Neonatal Rat Model
Received: 2016.02.21 Accepted: 2016.04.21 Published: 2016.12.23
Authors’ ABCDE Contribution: Jinglei Xiao Study Design A AB Yongchang Tan Data Collection B BD Yinjiao Li Statistical Analysis C Data Interpretation AFG D Yan Luo Manuscript Preparation E Literature Search F Funds Collection G
Department of Anesthesiology, Ruijin Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, P.R. China
Corresponding Author: Source of support:
Yan Luo, e-mail:
[email protected] This work was supported by Grants 81371219 from the National Natural Science Foundation of China and 201440440 from the Shanghai Health Bureau Scientific Research Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
Background:
Material/Methods:
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Conclusions:
Brain injuries induced by hypoxia-ischemia in neonates contribute to increased mortality and lifelong neurological dysfunction. The specific PKR inhibitor C16 has been previously demonstrated to exert a neuroprotective role in adult brain injuries. However, there is no recent study available concerning its protective role in hypoxia-ischemia-induced immature brain damage. Therefore, we investigated whether C16 protects against neonatal hypoxia-ischemia injuries in a neonatal rat model. Postnatal day 7 (P7) rats were used to establish classical hypoxia-ischemia animal models, and C16 postconditioning with 100 ug/kg was performed immediately after hypoxia. Western blot analysis was performed to quantify the phosphorylation of the PKR at 0 h, 3 h, 6 h, 12 h, 24 h, and phosphorylation of NF-kB 24h after hypoxia exposure. The TTC stain for infarction area and TUNEL stain for apoptotic cells were assayed 24 h after the brain hypoxia. Gene expression of IL-1b, IL-6, and TNF-a was performed at 3 h, 6 h, 12 h, and 24 h. The level of PKR autophosphorylation was increased dramatically, especially at 3 h (C16 group vs. HI group, P
