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.
Kojima
Toshio
T
Computational Systems Biology Research Group, Advanced Science Institute, RIKEN 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan. tkojima@riken.jp
Ueda
Yuto
Y
Adati
Naoki
N
Kitamoto
Aya
A
Sato
Akira
A
Huang
Ming-Chih
MC
Noor
Jesmine
J
Sameshima
Hiroshi
H
Ikenoue
Tsuyomu
T
D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000494:pharmacology*; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004195:Disease Models, Animal; D000077553:Edaravone; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology; D053263:Gene Regulatory Networks / Q000187:drug effects* / Q000502:physiology; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar
D000975:Antioxidants; D016166:Free Radical Scavengers; D018696:Neuroprotective Agents; D000077553:Edaravone; D000983:Antipyrine