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

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.