Brain genomics of intracerebral hemorrhage

J Cereb Blood Flow Metab. 2006 Feb;26(2):230-52. doi: 10.1038/sj.jcbfm.9600183.


After intracerebral hemorrhage (ICH), many changes of gene transcription occur that may be important because they will contribute to understanding mechanisms of injury and recovery. Therefore, gene expression was assessed using Affymetrix microarrays in the striatum and the overlying cortex at 24 h after intracranial infusions of blood into the striatum of adult rats. Intracerebral hemorrhage regulated 369 of 8,740 transcripts as compared with saline-injected controls, with 104 regulated genes shared by the striatum and cortex. There were 108 upregulated and 126 downregulated genes in striatum, and 170 upregulated and 69 downregulated genes in the cortex. Real-time reverse transcriptase-polymerase chain reaction (RT-PCR) confirmed upregulation of IL-1-beta, Lipcortin 1 (annexin) and metallothionein 1,2, and downregulation of potassium voltage-gated channel, shaker-related subfamily, beta member 2 (Kcnab2). Of the functional groups of genes modulated by ICH, many metabolism and signal-transduction-related genes decreased in striatum but increased in adjacent cortex. In contrast, most enzyme, cytokine, chemokine, and immune response genes were upregulated in both striatum and in the cortex after ICH, likely in response to foreign proteins from the blood. A number of these genes may contribute to brain edema and cellular apoptosis caused by ICH. In addition, downregulation of growth factor pathways and the phosphatidylinositol 3-kinase (PI3K)/Akt pathway could also contribute to perihematoma cell death/apoptosis. Intracerebral hemorrhage-related downregulation of GABA-related genes and potassium channels might contribute to perihematoma cellular excitability and increased risk of post-ICH seizures. These genomic responses to ICH potentially provide new therapeutic targets for treatment.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Annexin A1 / genetics
  • Annexin A1 / metabolism
  • Brain / metabolism
  • Brain / physiology*
  • Cerebral Hemorrhage / genetics*
  • Cluster Analysis
  • Disease Models, Animal
  • Down-Regulation
  • Gene Expression Profiling*
  • Genomics*
  • Growth Substances / genetics
  • Growth Substances / metabolism
  • Interleukin-1 / genetics
  • Interleukin-1 / metabolism
  • Male
  • Metallothionein / genetics
  • Metallothionein / metabolism
  • Oligonucleotide Array Sequence Analysis / methods
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Potassium Channels, Voltage-Gated / genetics
  • Potassium Channels, Voltage-Gated / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Transcription, Genetic
  • Up-Regulation
  • gamma-Aminobutyric Acid / genetics
  • gamma-Aminobutyric Acid / metabolism


  • Annexin A1
  • Growth Substances
  • Interleukin-1
  • Kcnab2 protein, rat
  • Potassium Channels, Voltage-Gated
  • gamma-Aminobutyric Acid
  • Metallothionein
  • Phosphatidylinositol 3-Kinases