Genomic profiles of damage and protection in human intracerebral hemorrhage.
|Title||Genomic profiles of damage and protection in human intracerebral hemorrhage.|
|Publication Type||Journal Article|
|Year of Publication||2008|
|Authors||Carmichael, TS, Vespa PM, Saver JL, Coppola G, Geschwind DH, Starkman S, Miller CM, Kidwell CS, Liebeskind DS, Martin NA|
|Journal||Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism|
|Date Published||2008 Nov|
|Keywords||Animals, Brain, Cerebral Hemorrhage, Clinical Trials as Topic, Disease Models, Animal, Gene Expression Profiling, Gene Expression Regulation, Humans, Magnetic Resonance Imaging, Mice, Nerve Tissue Proteins, Nucleic Acid Hybridization, Oligonucleotide Array Sequence Analysis, RNA, Safety, Surgical Procedures, Minimally Invasive|
Intracerebral hemorrhage (ICH) produces a high rate of death and disability. The molecular mechanisms of damage in perihematomal tissue in humans have not been systematically characterized. This study determines the gene expression profile and molecular networks that are induced in human perihematomal tissue through molecular analysis of tissue obtained from endoscopic clot evacuation. Differentially expressed genes and their cellular origin were confirmed in a mouse model of ICH. A total of 624 genes showed altered regulation in human ICH. Bioinformatic analysis shows that these genes form interconnected networks of proinflammatory, anti-inflammatory, and neuronal signaling cascades. Intracerebral hemorrhage evokes coordinated upregulation of proinflammatory signaling through specific cytokines and chemokines and their downstream molecular pathways. Anti-inflammatory networks are also induced by ICH, including annexins A1 and A2 and transforming growth factor beta (TGFbeta) and their intracellular cascades. Intracerebral hemorrhage downregulates many neuronal signaling systems, including the N-methyl-D-aspartic acid (NMDA) receptor complex and membrane ion channels. Select portions of these molecular networks were confirmed in the mouse, and the proteins in a subset of these networks localized to subsets of neurons, oligodendrocytes, or leukocytes. These inflammatory and anti-inflammatory networks interact at several key points in neutrophil signaling, apoptotic cell death, and protease responses, and indicate that secondary damage in ICH activates opposing molecular systems.
|Alternate Journal||J. Cereb. Blood Flow Metab.|