Journal of Molecular Neuroscience

, Volume 49, Issue 2, pp 320–327

Comprehensive Gene Expression Analysis of Cerebral Cortices from Mature Rats After Neonatal Hypoxic–Ischemic Brain Injury

  • Toshio Kojima
  • Yuto Ueda
  • Akira Sato
  • Hiroshi Sameshima
  • Tsuyomu Ikenoue
Article

DOI: 10.1007/s12031-012-9830-5

Cite this article as:
Kojima, T., Ueda, Y., Sato, A. et al. J Mol Neurosci (2013) 49: 320. doi:10.1007/s12031-012-9830-5

Abstract

Neonatal hypoxic–ischemic (HI) encephalopathy can lead to severe brain damage and is a common cause of neurological handicaps in adulthood. To elucidate the molecular events occurring in cerebral cortices of mature rats (8 weeks old) after neonatal HI brain insult, we performed comprehensive gene expression and gene network analyses using a DNA microarray system (Agilent 4x44K). A rat model of neonatal HI encephalopathy (Rice model) was obtained by unilateral ligation of the common carotid artery of 7-day-old rats with hypoxia (exposure to 8 % oxygen). Due to the HI insult-related breakdown of the ipsilateral hemisphere in the brain, RNAs were prepared from the contralateral cerebral cortices of 8-week-old rats and analyzed by DNA microarray. Biofunctional analysis of differentially regulated genes revealed that many upregulated genes were related to cell death signaling, such as the arachidonic acid cascade. In contrast, many downregulated genes were related to gene expression, reflecting progressive damage by the HI insult, even within the contralateral cerebral hemisphere.

Keywords

Neonatal hypoxic–ischemic encephalopathyGene expressionDNA microarrayGene network

Supplementary material

12031_2012_9830_MOESM1_ESM.xlsx (15 kb)
Supplementary Table S1Upregulated probes (XLSX 15 kb)
12031_2012_9830_MOESM2_ESM.xlsx (19 kb)
Supplementary Table S2Downregulated probes (XLSX 18 kb)
12031_2012_9830_MOESM3_ESM.pptx (1.4 mb)
Supplementary Fig. S1Gene network analysis of upregulated genes in HI encephalopathy. Networks were identified using the Ingenuity program. In each network, solid lines indicate direct interactions, dashed lines indicate indirect interactions, lines without arrowheads indicate binding, and arrows connecting 2 genes indicate directional functionality, whereby 1 gene acts on the other based on the direction of the arrow. Node shapes represent different gene families/groups: square (solid line), cytokine; square (dashed line), growth factor; rectangle (solid line), G-protein coupled receptor; rectangle (dashed line), ion channel; double circle, group or complex; triangle, kinase; diamond (vertical), enzyme; diamond (horizontal), peptidase; hexagon, translation regulator; trazoid, transporter; oval (horizontal), transcription regulator; and oval (vertical), transmembrane receptor. Proteins identified in this analysis are shaded. (PPTX 1400 kb)
12031_2012_9830_MOESM4_ESM.pptx (1.5 mb)
Supplementary Fig. S2Gene network analysis of the downregulated genes in HI encephalopathy. (PPTX 1578 kb)

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Toshio Kojima
    • 1
    • 2
  • Yuto Ueda
    • 3
  • Akira Sato
    • 2
  • Hiroshi Sameshima
    • 4
  • Tsuyomu Ikenoue
    • 4
  1. 1.Research Equipment CenterHamamatsu University School of MedicineHamamatsuJapan
  2. 2.Computational Systems Biology Research GroupAdvanced Science InstituteYokohamaJapan
  3. 3.Section of Psychiatry, Department of Clinical Neuroscience, Faculty of MedicineUniversity of MiyazakiMiyazakiJapan
  4. 4.Section of Obstetrics and Gynecology, Department of Reproductive and Developmental Medicine, Faculty of MedicineUniversity of MiyazakiMiyazakiJapan