Transcriptomics,Genomics

Dataset Information

28

Network analysis of differentially expressed genes in a rat model of neonatal HI encephalopathy +/- antioxidant


ABSTRACT: Neonatal hypoxic-ischemic (HI) encephalopathy can lead to severe brain damage, and is a common cause of neurological handicaps in adulthood. The modified Levine method (Rice model) has been widely used as an animal model of this condition, which can be rescued by the administration of an antioxidant such as 3-methyl-1-phenyl-2-pyrazolin-5-one (MCI-186). In the present study, by using the Rice model, we performed comprehensive gene expression and gene network analyses of neonatal HI brain insult with and without MCI-186 administration via a DNA microarray to help elucidate the molecular events responsible for the selective vulnerability of neurons to an HI insult and the underlying mechanisms of the effect of MCI-186 on the pathophysiological events. A large difference in gene expression was observed between the Rice model and the control. By performing a clustering analysis of the gene expression pattern after the HI brain insult, we found the following 3 clusters: (i) a cluster of strongly upregulated genes mainly consisting of genes related to immune responses; (ii) a cluster of mildly upregulated genes mainly consisting of genes related to cellular movement, growth and proliferation, and cell death; and (iii) a cluster of downregulated genes mainly consisting of genes related to neuronal activity. The effect of MCI-186 administration on gene expression was much less than and contrary to that of the HI brain insult. The genes upregulated and downregulated on MCI-186 administration were closely related to neuronal activity and immune responses, respectively, thereby reflecting the protective effect of MCI-186 on an HI brain insult. Overall design: Seven-day-old Wistar rats were assigned to two groups: control group and Rice group. The Rice group rats were subjected to a modified Levine’s procedure to produce the HI brain injury. Each rat was anesthetized with ether, and the left carotid artery was sectioned between double ligatures with 4-0 surgical silk. The rats were allowed to recover for 1–2 h and then exposed to 1 h of hypoxia in a plastic chamber, which was perfused with a mixture of humidified 8% oxygen balanced with nitrogen. The temperature inside the chamber was maintained at 33 °C, the usual temperature while huddling with the mother. Immediately after removal from the hypoxia chamber, the pups were intraperitoneally injected with 100 ul normal saline or 9 mg/kg MCI-186 dissolved in normal saline. The injection was repeated after 30 min. The control group rats were not exposed to HI brain insult but received an intraperitoneal injection of 100 ul saline or 9 mg/kg MCI-186 dissolved in normal saline. There were three pups per condition in both the groups. The cerebral cortexes ipsilateral to the HI brain insult and those of the same side of the control animals were used for the experiment.

INSTRUMENT(S): Agilent-014879 Whole Rat Genome Microarray 4x44K G4131F (Probe Name version)

SUBMITTER: Toshio Kojima 

PROVIDER: GSE18356 | GEO | 2010-03-05

SECONDARY ACCESSION(S): PRJNA118109

REPOSITORIES: GEO

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Publications

Gene network analysis to determine the effects of antioxidant treatment in a rat model of neonatal hypoxic-ischemic encephalopathy.

Kojima Toshio T   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  

Journal of molecular neuroscience : MN 20100227 2


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  ...[more]

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