Global gene expression in the immature brain after hypoxia-ischemia

• Ischemia induces a complex response of differentially expressed genes in the brain. In order to understand the specific mechanisms of injury in the developing brain, it is important to obtain information on global changes in the transcriptome after neonatal hypoxia-ischemia. In this study, oligonucleotide arrays were used to investigate genomic changes at 2, 8, 24, and 72 hours after neonatal hypoxia-ischemia, which was induced in 9-day-old mice by left carotid artery ligation followed by hypoxia (10% O2). In total, 343 genes were differentially expressed in cortex, hippocampus, thalamus, and striatum 2 to 72 hours after hypoxia-ischemia, when comparing ipsilateral with contralateral hemispheres and with controls, using the significance analysis for microarrays. A total of 283 genes were upregulated and 60 were downregulated, and 94% of the genes had not previously been shown after neonatal hypoxia-ischemia. Genes related to transcription factors and metabolism had mostly upregulated transcripts, whereas most downregulated genes belonged to the categories of ion and vesicular transport and signal transduction. Genes involved in transcription, stress, and apoptosis were induced early after the insult, and many new genes that may play important roles in the pathophysiology of neonatal hypoxia-ischemia were identified.

Nyckelord

Aging/*genetics

Animals

Animals

Newborn

Apoptosis/genetics

Cytoskeleton/genetics

*Gene Expression Profiling

Gene Expression Regulation

Growth Substances/genetics

Hormones/genetics

Hypoxia-Ischemia

Brain/*genetics

Mice

Mice

Inbred C57BL

Neurotransmitter Agents/genetics

Oligonucleotide Array Sequence Analysis

Protein Transport

RNA

Messenger/analysis/genetics

Signal Transduction

Stress/genetics

Synapses/genetics

Transcription

Genetic/genetics

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