Published Online
on September 30, 2004

A more recent version of this article appeared on November 1, 2004

This Article Full Text (PDF) All Versions of this Article: 35/11_suppl_1/2683    most recent 01.STR.0000143735.89281.bbv1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Stenzel-Poore, M. P. Articles by Simon, R. P. Search for Related Content PubMed PubMed Citation Articles by Stenzel-Poore, M. P. Articles by Simon, R. P. Related Collections Acute coronary syndromes

Submitted on June 9, 2004
Accepted on June 9, 2004

Genomics of Preconditioning

Mary P. Stenzel-Poore PhD^*; Susan L. Stevens BS; and Roger P. Simon MD

From the Department of Molecular Microbiology and Immunology (M.P.S.-P., S.L.S.), Oregon Health & Science University, Portland, Ore; and the Robert S. Dow Neurobiology Laboratories (R.P.S.), Legacy Research, Portland, Ore.

^* To whom correspondence should be addressed. E-mail: poorem{at}OHSU.edu.

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.

Key words: gene expression • middle cerebral artery occlusion

This article has been cited by other articles:

				R. Meller The Role of the Ubiquitin Proteasome System in Ischemia and Ischemic Tolerance Neuroscientist, June 1, 2009; 15(3): 243 - 260. [Abstract] [PDF]

				T. P. Obrenovitch Molecular Physiology of Preconditioning-Induced Brain Tolerance to Ischemia Physiol Rev, January 1, 2008; 88(1): 211 - 247. [Abstract] [Full Text] [PDF]

				M. P. Stenzel-Poore, S. L. Stevens, J. S. King, and R. P. Simon Preconditioning Reprograms the Response to Ischemic Injury and Primes the Emergence of Unique Endogenous Neuroprotective Phenotypes: A Speculative Synthesis Stroke, February 1, 2007; 38(2): 680 - 685. [Abstract] [Full Text] [PDF]

				G. Faraco, T. Pancani, L. Formentini, P. Mascagni, G. Fossati, F. Leoni, F. Moroni, and A. Chiarugi Pharmacological Inhibition of Histone Deacetylases by Suberoylanilide Hydroxamic Acid Specifically Alters Gene Expression and Reduces Ischemic Injury in the Mouse Brain Mol. Pharmacol., December 1, 2006; 70(6): 1876 - 1884. [Abstract] [Full Text] [PDF]

				M. Mogi, J.-M. Li, J. Iwanami, L.-J. Min, K. Tsukuda, M. Iwai, and M. Horiuchi Angiotensin II Type-2 Receptor Stimulation Prevents Neural Damage by Transcriptional Activation of Methyl Methanesulfonate Sensitive 2 Hypertension, July 1, 2006; 48(1): 141 - 148. [Abstract] [Full Text] [PDF]

				T. Kaneko, K. Yokoyama, and K. Makita Late preconditioning with isoflurane in cultured rat cortical neurones Br. J. Anaesth., November 1, 2005; 95(5): 662 - 668. [Abstract] [Full Text] [PDF]