Brain genomics of intracerebral hemorrhage.
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.
Lu
Aigang
A
MIND Institute and Department of Neurology, University of California at Davis, Sacramento, California 95817, USA. aiglu@ucdavis.edu
Tang
Yang
Y
Ran
Ruiqiong
R
Ardizzone
Timothy L
TL
Wagner
Kenneth R
KR
Sharp
Frank R
FR
D000818:Animals; D017305:Annexin A1 / Q000235:genetics / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000502:physiology*; D002543:Cerebral Hemorrhage / Q000235:genetics*; D016000:Cluster Analysis; D004195:Disease Models, Animal; D015536:Down-Regulation; D020869:Gene Expression Profiling; D023281:Genomics; D006133:Growth Substances / Q000235:genetics / Q000378:metabolism; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism; D008297:Male; D008668:Metallothionein / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014158:Transcription, Genetic; D015854:Up-Regulation; D005680:gamma-Aminobutyric Acid / Q000235:genetics / Q000378:metabolism
D017305:Annexin A1; D006133:Growth Substances; D007375:Interleukin-1; C426239:Kcnab2 protein, rat; D024642:Potassium Channels, Voltage-Gated; D005680:gamma-Aminobutyric Acid; D008668:Metallothionein; D019869:Phosphatidylinositol 3-Kinases