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Oxidative Medicine and Cellular Longevity
Volume 2018 (2018), Article ID 9797146, 10 pages
Research Article

Granulocyte Colony-Stimulating Factor Alleviates Bacterial-Induced Neuronal Apoptotic Damage in the Neonatal Rat Brain through Epigenetic Histone Modification

1Department of Pediatrics, E-DA Hospital, Kaohsiung, Taiwan
2School of Medicine, I-Shou University, Kaohsiung, Taiwan
3Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
4Joint Biobank, Office of Human Research, Taipei Medical University, Taipei, Taiwan
5Research Center for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
6Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

Correspondence should be addressed to San-Nan Yang

Received 30 August 2017; Revised 7 November 2017; Accepted 23 November 2017; Published 1 February 2018

Academic Editor: Partha Mukhopadhyay

Copyright © 2018 Yung-Ning Yang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Bacterial meningitis during the perinatal period may cause long-term neurological deficits. The study investigated whether bacterial lipopolysaccharide (LPS) derived from E. coli. led to neuronal apoptosis with an impaired performance of long-term cognitive function involving the activation of histone modification in the TNF-α gene promoter. Further, we looked into the therapeutic efficacy of granulocyte colony-stimulating factor (G-CSF) in a neonatal brain suffering from perinatal bacterial meningitis. We applied the following research techniques: neurobehavioral tasks, confocal laser microscopy, chromatin immunoprecipitation, and Western blotting. At postnatal day 10, the animals were subjected to LPS and/or G-CSF. The target brain tissues were then collected at P17. Some animals (P45) were studied using neurobehavioral tasks. The LPS-injected group revealed significantly increased expression of NF-κB phosphorylation and trimethylated H3K4 in the TNFA gene promoter locus. Furthermore, the caspase-3, neuronal apoptosis expression, and an impaired performance in cognitive functions were also found in our study. Such deleterious outcomes described above were markedly alleviated by G-CSF therapy. This study suggests that selective therapeutic action sites of G-CSF through epigenetic regulation in the TNFA gene promoter locus may exert a potentially beneficial role for the neonatal brain suffering from perinatal bacterial-induced meningitis.