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Gene Expression Profiling in Ischemic Brain Injury and Ischemic Tolerance

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Handbook of Neurochemistry and Molecular Neurobiology
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Abstract:

Potent endogenous mechanisms of neuroprotection are encoded in the genome, and the expression of a subset of these genes helps to determine whether cells survive ischemia. A genomic approach may identify and characterize these genes and the neuroprotective pathways through which their protein products operate. Identification of gene products that are endogenous neuroprotectants contributes significantly to our understanding of the pathophysiology of ischemic neuronal injury and would point the way toward new therapeutic approaches to stroke and related disorders such as traumatic brain injury. Here we review a strategy for discovering neuroprotective genes in ischemia by the use of mouse models of ischemic tolerance and microarray analysis to identify genes that are transcriptionally regulated in tolerance. We provide Affymetrix microarray analysis of an ischemic tolerance data set and review in detail the approach to genomic screening.

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References

  • Abe H, Nowak TS Jr. 1996. Gene expression and induced ischemic tolerance following brief insults. Acta Neurobiol Exp 56: 3–8.

    CAS  Google Scholar 

  • Abe K, Kawagoe J, Itoyama Y, Kogure K. 1996. Isolation of an ischemia‐induced gene and early disturbance of mitochondrial DNA expression after transient forebrain ischemia. Adv Neurol 71: 485–503.

    CAS  PubMed  Google Scholar 

  • An G, Lin TN, Liu JS, Xue JJ, He YY, et al. 1993. Expression of c‐fos and c‐jun family genes after focal cerebral ischemia. Ann Neurol 33: 457–464.

    Article  CAS  PubMed  Google Scholar 

  • Barone FC, White RF, Spera PA, Ellison J, Currie RW, et al. 1998. Ischemic preconditioning and brain tolerance: temporal histological and functional outcomes, protein synthesis requirement, and interleukin‐1 receptor antagonist and early gene expression. Stroke 29:1937–1950; discussion 1950–1931.

    Article  CAS  PubMed  Google Scholar 

  • Bassett D, Eisen M, Boguski M. 1999. Gene expression informatics—it's all in your mine. Nat Genet 21 (1 Suppl.): 51–55.

    Article  CAS  PubMed  Google Scholar 

  • Bergeron M, Gidday JM, Yu AY, Semenza GL, Ferriero DM, et al. 2000. Role of hypoxia‐inducible factor‐1 in hypoxia‐induced ischemic tolerance in neonatal rat brain. Ann Neurol 48: 285–296.

    Article  CAS  PubMed  Google Scholar 

  • Bernaudin M, Tang Y, Reilly M, Petit E, Sharp FR. 2002. Brain genomic response following hypoxia and re‐oxygenation in the neonatal rat: identification of genes that might contribute to hypoxia‐induced ischemic tolerance. J Biol Chem 26: 26.

    Google Scholar 

  • Brown M, Grundy W, Lin D, Cristianini N, Sugnet C, et al. 2000. Knowledge‐based analysis of microarray gene expression data by using support vector machines. PNAS 97: 262–267.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen J, Graham S, Chan P, Lan J, Zhou R, et al. 1995. Bcl‐2 is expressed in neurons that survive focal ischemia in the rat. Neuroreport 6: 394–398.

    Article  CAS  PubMed  Google Scholar 

  • Chen J, Graham SH, Zhu RL, Simon RP. 1996a. Stress proteins and tolerance to focal cerebral ischemia. J Cereb Blood Flow Metab 16: 566–577.

    Article  CAS  PubMed  Google Scholar 

  • Chen J, Zhu RL, Nakayama M, Kawaguchi K, Jin K, et al. 1996b. Expression of the apoptosis‐effector gene, Bax, is up‐regulated in vulnerable hippocampal CA1 neurons following global ischemia. J Neurochem 67: 64–71.

    Article  CAS  PubMed  Google Scholar 

  • Chen J, Simon RP, Nagayama T, Zhu R, Loeffert JE, et al. 2000. Suppression of endogenous bcl‐2 expression by antisense treatment exacerbates ischemic neuronal death. J Cereb Blood Flow Metab 20: 1033–1039.

    Article  CAS  PubMed  Google Scholar 

  • Cheng J, Sun S, Tracy A, Hubbell E, Morris J, et al. 2004. NetAffx Gene Ontology Mining Tool: a visual approach for microarray data analysis. Bioinformatics 20: 1462–1463.

    Article  CAS  PubMed  Google Scholar 

  • Denhardt DT, Lopez CA, Rollo EE, Hwang SM, An XR, et al. 1995. Osteopontin‐induced modifications of cellular functions. Ann N Y Acad Sci 760: 127–142.

    Article  CAS  PubMed  Google Scholar 

  • Dudoit S, Young Y, Callow M, Speed T. 2000. Statistical methods for identifying differentially expressed genes in replicated cDNA microarray experiments. Technical Report 578.

    Google Scholar 

  • Eisen M, Spellman P, Brown P, Botstein D. 1998. Cluster analysis and display of genome‐wide expression patterns. Proc Natl Acad Sci USA 95: 14863–14868.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ellison JA, Velier JJ, Spera P, Jonak ZL, Wang X, et al. 1998.Osteopontin and its integrin receptor alpha(v)beta3 are upregulated during formation of the glial scar after focal stroke. Stroke 29:1698–1706; discussion 1707.

    Article  CAS  PubMed  Google Scholar 

  • Ermolaeva O, Rastogi M, Pruitt K, Schuler G, Bittner M, et al. 1998. Data management and analysis for gene expression arrays. Nat Genet 20: 19–23.

    Article  CAS  PubMed  Google Scholar 

  • Ferea T, Brown P. 1999. Observing the living genome. Curr Opin Genet Dev 9: 715–722.

    Article  CAS  PubMed  Google Scholar 

  • Furey T, Cristianini N, Duffy N, Bednarski D, Schummer M, et al. 2000. Support vector machine classification and validation of cancer tissue samples using microarray expression data. Bioinformatics 16: 906–914.

    Article  CAS  PubMed  Google Scholar 

  • Getz G, Levine E, Domany E. 2000. Coupled two‐way clustering analysis of gene microarray data. Proc Natl Acad Sci USA 97: 12079–12084.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Guo H, Cai CQ, Schroeder RA, Kuo PC. 2001. Osteopontin is a negative feedback regulator of nitric oxide synthesis in murine macrophages. J Immunol 166: 1079–1086.

    Article  CAS  PubMed  Google Scholar 

  • Hastie T, Tibshirani R, Eisen M, Alizadeh A, Levy R, et al. 2000. ‘Gene shaving' as a method for identifying distinct sets of genes with similar expression patterns. Genome Biology 1: RESEARCH0003.

    Google Scholar 

  • Hilsenbeck S, Friedrichs W, Schiff R, O'Connell P, Hansen R, et al. 1999. Statistical analysis of array expression data as applied to the problem of tamoxifen resistance. J Narl Cancer Inst 91: 453–459.

    Article  CAS  Google Scholar 

  • Hochachka PW, Buck LT, Doll CJ, Land SC. 1996. Unifying theory of hypoxia tolerance: molecular/metabolic defense and rescue mechanisms for surviving oxygen lack. Proc Natl Acad Sci USA 93: 9493–9498.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Holter N, Mitra M, Martian A, Cieplak M, Banavar J, et al. 2000. Fundamental patterns underlying gene expression profiles: simplicity from complexicity. Proc Natl Acad Sci USA 97: 8409–8414.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hubbell E, Liu WM, Mei R. 2002. Robust estimators for expression analysis. Bioinformatics 18: 1585–1592.

    Article  CAS  PubMed  Google Scholar 

  • Irizarry RA, Hobbs B, Collin F, Beazer‐Barclay YD, Antonellis KJ, et al. 2003. Exploration, normalization, and summaries of high density oligonucleotide array probe level data. Biostatistics 4: 249–264.

    Article  PubMed  Google Scholar 

  • Kato H, Kogure K, Araki T, Liu XH, Kato K, et al. 1995. Immunohistochemical localization of superoxide dismutase in the hippocampus following ischemia in a gerbil model of ischemic tolerance. J Cereb Blood Flow Metab 15: 60–70.

    Article  CAS  PubMed  Google Scholar 

  • Kerr M, Martin M, Churchill G. 2000. Analysis of variance for gene expression microarray data. Submitted manuscript (http://www.jax.org/reserach/churchill/pubs/index.html).

  • Khan J, Simon R, Bittner M, Chen Y, Leighton S, et al. 1998. Gene expression profiling of aleveolar rhabdomyosrcoma with cDNA microarrays. Cancer Res 58: 5009–5013.

    CAS  PubMed  Google Scholar 

  • Kobayashi S, Harris VA, Welsh FA. 1995. Spreading depression induces tolerance of cortical neurons to ischemia in rat brain. J Cereb Blood Flow Metab 15: 721–727.

    Article  CAS  PubMed  Google Scholar 

  • Lazzeroni L, Owen A. 2000. Plaid models for gene expression data. Submitted manuscript (http://www‐stat.stanford.edu/∼owen/reports/).

  • Lemkin P, Thornwall G, Walton K, Hennighausen L. 2000. The microarray explorer tool for data mining of cDNA microarrays: application for the mammary gland. Nucleic Acids Res 15: 4452–4459.

    Article  Google Scholar 

  • Li C, Wong W. 2001. Model‐based analysis of oligonucleotide arrays: expression index computation and outlier detection. PNAS 98: 31–36.

    Article  CAS  PubMed  Google Scholar 

  • Lipshutz R, Fodor S, Gingeras T, Lockhart D. 1999. High density synthetic oligonucleotide arrays. Suppl Nat Genet 21: 20–24.

    Article  CAS  PubMed  Google Scholar 

  • Liu G, Loraine AE, Shigeta R, Cline M, Cheng J, et al. 2003. NetAffx: affymetrix probesets and annotations. Nucleic Acids Res 31: 82–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu WM, Mei R, Di X, Ryder TB, Hubbell E, et al. 2002. Analysis of high density expression microarrays with signed‐rank call algorithms. Bioinformatics 18: 1593–1599.

    Article  CAS  PubMed  Google Scholar 

  • Lockhart DJ, Barlow C. 2001. Expressing what's on your mind: DNA arrays and the brain. Nat Rev 2.

    Google Scholar 

  • Loftus S, Chen Y, Gooden G, Ryan J, Birznieks G, et al. 1999. Informatic selection of a neural crest‐melanocyte cDNA set for microarray analysis. PNAS 96: 9277–9280.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Manduchi E, Grant G, McKenzie S, Overton G, Surrey S, et al. 2000. Generation of patterns from gene expression data by assigning confidence to differentially expressed genes. Bioinformatics 16: 685–698.

    Article  CAS  PubMed  Google Scholar 

  • Meller R, Stevens SL, Minami M, Cameron JA, King S, et al. 2005. Neuroprotection by osteopontin in stroke. J Cereb Blood Flow Metab 25(2): 217–225.

    Article  CAS  Google Scholar 

  • Michaels G, Carr D, Askenazi M, Fuhrman S, Wen X, et al. 1998. Cluster analysis and data visualization of large‐scale gene expression data. Pac Symp Biocomput 1998: 42–53.

    Google Scholar 

  • Mouse Genome Database, Mouse Genome Infomatics Website. 2002a. The Jackson Laboratory, Bar Harbor, Maine. World Wide Web (http://www.informatiacs.jax.org/).

  • Newton M, Kendziorski C, Richmond C, Blattner F, Tsui K. 2000. On differential variability of expression ratios: improving statistical inference about gene expression changes from microarray data. Technical Report #139. Department of Biostatistics, Medical Informatics, University of Wisconsin Madison. To appear in the Journal of Computational Biology.

    Google Scholar 

  • Ohtsuki T, Matsumoto M, Kuwabara K, Kitagawa K, Suzuki K, et al. 1992. Influence of oxidative stress on induced tolerance to ischemia in gerbil hippocampal neurons. Brain Res 599: 246–252.

    Article  CAS  PubMed  Google Scholar 

  • Pruitt K, Maglott D. 2001. RefSeq and LocusLink: NCBI gene‐centered resources. Nucleic Acids Res 29: 137–140.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rajdev S, Hara K, Kokubo Y, Mestril R, Dillmann W, et al. 2000. Mice overexpressing rat heat shock protein 70 are protected against cerebral infarction. Ann Neurol 47: 782–791.

    Article  CAS  PubMed  Google Scholar 

  • Scatena M, Almeida M, Chaisson ML, Fausto N, Nicosia RF, et al. 1998. NF‐kappaB mediates alphavbeta3 integrin‐induced endothelial cell survival. J Cell Biol 141: 1083–1093.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schadt EE, Li C, Ellis B, Wong WH. 2001. Feature extraction and normalization algorithms for high‐density oligonucleotide gene expression array data. J Cell Biochem Suppl 37: 120–125.

    Article  PubMed  CAS  Google Scholar 

  • Schuler G. 1997. Pieces of the puzzle: expressed sequence tags and the catalog of human genes. J Mol Med 75: 694–698.

    Article  CAS  PubMed  Google Scholar 

  • Shimazaki K, Ishida A, Kawai N. 1994. Increase in bcl‐2 oncoprotein and the tolerance to ischemia‐induced neuronal death in the gerbil hippocampus. Neurosci Res 20: 95–99.

    Article  CAS  PubMed  Google Scholar 

  • Shimizu S, Nagayama T, Jin KL, Zhu L, Loeffert JE, et al. 2001. Bcl‐2 antisense treatment prevents induction of tolerance to focal ischemia in the rat brain. J Cereb Blood Flow Metab 21: 233–243.

    Article  CAS  PubMed  Google Scholar 

  • Stanford Online Universal Resource for Clones and ESTs (Source) Web Site. 2002b. Genetics Department, Stanford University (http://genome‐www5.stanford.edu/cgi‐bin/SMD/source).

  • Stenzel‐Poore MP, Stevens SL, Xiong Z, Lessov NS, Harrington CA, et al. 2003. Effect of ischaemic preconditioning on genomic response to cerebral ischaemia: similarity to neuroprotective strategies in hibernation and hypoxia‐tolerant states. Lancet 362: 1028–1037.

    Article  PubMed  CAS  Google Scholar 

  • Tanabe L, Scherf U, Smith L, Lee J, Hunter L, et al. 2000. MedMiner: an internet text‐mining tool for biomedical information, with application to gene expression profiling. BioTechniques 27: 1210–1217.

    Article  Google Scholar 

  • Tsodikov A, Szabo A, Jones D. 2000. Adjustments and measures of differential expression for microarray data. Bioinformatics. 18(2): 251-260.

    Google Scholar 

  • Tusher V, Tibshirani R, Chu G. 2001. Significance analysis of microarrays applied to the ionizing radiation response. PNAS 98: 5116–5121.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang X, Louden C, Yue TL, Ellison JA, Barone FC, et al. 1998. Delayed expression of osteopontin after focal stroke in the rat. J Neurosci 18: 2075–2083.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang M. 1999. Large‐scale gene expression data analysis: a new challenge to computational biologists. Genome Res 9: 681–688.

    Article  CAS  PubMed  Google Scholar 

  • Zhang X, Cui SS, Wallace AE, Hannesson DK, Schmued LC, et al. 2002. Relations between brain pathology and temporal lobe epilepsy. J Neurosci 22: 6052–6061.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Harrington, C.A., Stevens, S., Stenzel‐Poore, M., Simon, R.P. (2007). Gene Expression Profiling in Ischemic Brain Injury and Ischemic Tolerance. In: Lajtha, A., Chan, P.H. (eds) Handbook of Neurochemistry and Molecular Neurobiology. Springer, New York, NY. https://doi.org/10.1007/978-0-387-30383-3_1

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