Genomics of preconditioning

Mary P. Stenzel-Poore, Susan L. Stevens, Roger P. Simon

Research output: Contribution to journalArticle

70 Scopus citations

Abstract

Brief episodes of ischemia can protect against subsequent damaging ischemic events; however, the molecular mechanisms responsible for protection are poorly understood. Identifying genes involved in this process could provide insight into cell survival and treatment of stroke. We developed a murine model of ischemic preconditioning and subsequent stroke and used gene expression profiling to identify genes that may be involved in neuroprotective pathways. Middle cerebral artery occlusions were performed in mice for 15 minutes, (preconditioning), 60 minutes (stroke), or 15 minutes, followed 72 hours later with 60 minutes (preconditioning plus stroke) of middle cerebral artery occlusions. RNA from a region of cortex that is protected by ischemic preconditioning was hybridized to oligonucleotide microarrays. Follow-up experiments used patch clamp to examine cell conductance in cultured neurons exposed to oxygen-glucose deprivation. Stroke, ischemic preconditioning, and ischemic preconditioning plus stroke all induced gene changes that overlapped little among conditions. Stroke induced robust upregulation of gene expression whereas preconditioning followed by stroke resulted in a marked downregulation. Genes upregulated by stroke suggested activation of stress/inflammatory pathways and increased metabolism and ion channel function. Preconditioning tended to decrease genes involved in these pathways. Follow-up experiments show that preconditioning decreased voltage-gated potassium currents in vitro and increased bleeding time. Preconditioning reprograms the response to ischemic injury via transcriptional changes that may suppress metabolic pathways and immune responses, reduce ion channel activity, and decrease blood coagulation. These changes resemble evolutionarily conserved responses to decreased blood flow and oxygen availability that occur during hibernation.

Original languageEnglish (US)
Pages (from-to)2683-2686
Number of pages4
JournalStroke
Volume35
Issue number11 SUPPL. 1
DOIs
StatePublished - Nov 1 2004

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Keywords

  • Gene expression
  • Middle cerebral artery occlusion

ASJC Scopus subject areas

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialized Nursing

Cite this

Stenzel-Poore, M. P., Stevens, S. L., & Simon, R. P. (2004). Genomics of preconditioning. Stroke, 35(11 SUPPL. 1), 2683-2686. https://doi.org/10.1161/01.STR.0000143735.89281.bb