Pathway and gene ontology based analysis of gene expression in a rat model of cerebral ischemic tolerance.

Full Abstract

Ischemic tolerance is a phenomenon whereby a sublethal ischemic insult [ischemic preconditioning (IPC)] provides robust protection against subsequent lethal ischemia. Activation of N-methyl-D-aspartate (NMDA) receptors and subsequent new gene transcription are required for tolerance. We utilized the NMDA antagonist, MK801, prior to the IPC stimulus to separate candidate genes from epiphenomenona. Rats were divided into four groups: vehicle/IPC (preconditioned), MK801/IPC (attenuated preconditioning), vehicle/sham (non-preconditioned), and MK801/sham (non-preconditioned). Hippocampi (5/group/time point) were harvested immediately after ischemia as well as 1, 4, and 24 h post-ischemia to profile gene expression patterns using microarray analyses. Extracted mRNAs were pooled and subsequently hybridized to Affymetrix arrays. In addition, groups of rats were sacrificed for Western blot analysis and histological studies. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and gene ontology (GO) analyses were used to identify functionally related groups of genes whose modulation was statistically significant, while hierarchical cluster analysis was used to visualize the fold expression within these groups. Significantly modulated pathways included: MAP kinase signaling pathway, Toll receptor pathway, TGF-beta signaling pathways, and pathways associated with ribosome function and oxidative phosphorylation. Our data suggest that the tolerant brain responds to subsequent ischemic stress by partially downregulating inflammatory and upregulating protein synthesis and energy metabolism pathways.

Author information

Author/s: Feng, Zheng (Z); Davis, Daniel P (DP); Sásik, Roman (R); Patel, Hemal H (HH); Drummond, John C (JC); Patel, Piyush M (PM);

Affiliation: Department of Anesthesiology, University of California, San Diego, USA.

Grants: 5P30 AI36214 (Agency:NIAID NIH HHS) ; NS047570-01 (Agency:NINDS NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

Journal: Brain research (Brain Res), published in Netherlands. (Language: eng)

Reference: 2007-Oct; vol 1177 (issue ) : pp 103-23

Dates: Created 2007/10/19; Completed 2008/01/15; Revised 2008/11/21;

PMID: 17916339, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals
Blotting, Western
Bone Morphogenetic Protein 7
Bone Morphogenetic Proteins - genetics
Brain Ischemia - genetics; pathology
Cluster Analysis
Computational Biology
Cyclooxygenase 2 - biosynthesis; genetics
Databases, Genetic
Fluorescent Antibody Technique, Direct
Gene Expression
Hippocampus - pathology

Associated Chemicals: Bmp7 protein, rat (0) ; Bone Morphogenetic Protein 7 (0) ; Bone Morphogenetic Proteins (0) ; Toll-Like Receptors (0) ; Transforming Growth Factor beta (0) ; Cyclooxygenase 2 (EC 1.14.99.1) ; Mitogen-Activated Protein Kinase Kinases (EC 2.7.1.-)

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