Brain genomics of intracerebral hemorrhage

Aigang Lu, Yang Tang, Ruiqiong Ran, Timothy L. Ardizzone, Kenneth R. Wagner, Frank R Sharp

Research output: Contribution to journalArticle

82 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)230-252
Number of pages23
JournalJournal of Cerebral Blood Flow and Metabolism
Volume26
Issue number2
DOIs
StatePublished - Feb 2006

Fingerprint

Cerebral Hemorrhage
Genomics
Brain
Genes
Down-Regulation
Phosphatidylinositol 3-Kinase
Apoptosis
Voltage-Gated Potassium Channels
Annexins
Metallothionein
Potassium Channels
Brain Edema
Reverse Transcriptase Polymerase Chain Reaction
Interleukin-1beta
Chemokines
gamma-Aminobutyric Acid
Blood Proteins
Real-Time Polymerase Chain Reaction
Signal Transduction
Intercellular Signaling Peptides and Proteins

Keywords

  • Apoptosis
  • Cerebral edema
  • Genomics
  • Intracerebral hemorrhage
  • Microarrays
  • Stroke

ASJC Scopus subject areas

  • Endocrinology
  • Neuroscience(all)
  • Endocrinology, Diabetes and Metabolism

Cite this

Brain genomics of intracerebral hemorrhage. / Lu, Aigang; Tang, Yang; Ran, Ruiqiong; Ardizzone, Timothy L.; Wagner, Kenneth R.; Sharp, Frank R.

In: Journal of Cerebral Blood Flow and Metabolism, Vol. 26, No. 2, 02.2006, p. 230-252.

Research output: Contribution to journalArticle

Lu, Aigang ; Tang, Yang ; Ran, Ruiqiong ; Ardizzone, Timothy L. ; Wagner, Kenneth R. ; Sharp, Frank R. / Brain genomics of intracerebral hemorrhage. In: Journal of Cerebral Blood Flow and Metabolism. 2006 ; Vol. 26, No. 2. pp. 230-252.
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