Gene Network Analysis to Determine the Effects of Antioxidant Treatment in a Rat Model of Neonatal Hypoxic-Ischemic Encephalopathy

• Published in: Journal of molecular neuroscience 2010-10, Vol.42 (2), p.154-161
• Main Authors: Kojima, Toshio, Ueda, Yuto, Adati, Naoki, Kitamoto, Aya, Sato, Akira, Huang, Ming-Chih, Noor, Jesmine, Sameshima, Hiroshi, Ikenoue, Tsuyomu
• Format: Article
• Language: English
• Subjects: Animal models; Animals; Animals, Newborn; Antioxidants; Antioxidants - pharmacology; Antipyrine - analogs & derivatives; Antipyrine - pharmacology; Apoptosis; Biomedical and Life Sciences; Biomedicine; Brain damage; Brain injury; Cell Biology; Cell death; Disease Models, Animal; DNA microarrays; Encephalopathy; Female; Free Radical Scavengers - pharmacology; Gene expression; Gene Regulatory Networks - drug effects; Gene Regulatory Networks - physiology; Hypoxia; Hypoxia-Ischemia, Brain - drug therapy; Hypoxia-Ischemia, Brain - genetics; Hypoxia-Ischemia, Brain - metabolism; Immune response; Ischemia; Medical research; Medicine; Neonates; Nervous system; Neurochemistry; Neurology; Neurons; Neuroprotective Agents - pharmacology; Neurosciences; Oligonucleotide Array Sequence Analysis; Oryza sativa; Pregnancy; Proteomics; Rats; Rats, Wistar; Traumatic brain injury
• ISSN: 0895-8696; 1559-1166
• DOI: 10.1007/s12031-010-9337-x

Neonatal hypoxic-ischemic (HI) encephalopathy can lead to severe brain damage, and is a common cause of neurological handicaps in adulthood. HI can be resolved by the administration of an antioxidant such as 3-methyl-1-phenyl-2-pyrazolin-5-one (MCI-186). In the present study, we performed comprehensive gene expression and gene network analyses using a DNA microarray to elucidate the molecular events responsible for the selective vulnerability of neurons in neonatal HI brain insult and to examine the underlying mechanisms of the effect of MCI-186 on the pathophysiological events in this condition. We used the modified Levine method (Rice model), which has been widely used as an animal model of this condition. A large difference in gene expression was observed between the Rice model and the control group. Up- and downregulated genes after the HI brain insult were mainly related to immune responses and cell death, and neuronal activity, respectively. The effect of MCI-186 administration on gene expression was much less than and contrary to that of the HI brain insult, reflecting the protective effect of MCI-186 in HI brain insult.