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ANESTHETIC PHARMACOLOGY

Isoflurane Modulates Genomic Expression in Rat Amygdala

Department of Anesthesiology and Neurological Surgery, State University of New York at Stony Brook, HSC University Hospital, Stony Brook, New York

Address correspondence and reprint requests to Ira J. Rampil, MS, MD, Department of Anesthesiology and Neurological Surgery, State University of New York at Stony Brook, L4-060 HSC University Hospital, 100 East Loop Road, Stony Brook, NY 11794-8480. Address e-mail to ira.rampil{at}sunysb.edu.

General anesthesia, at a minimum, provides amnesia and unresponsiveness. Although anesthetics have many modulatory effects on neuronal ionophore protein complexes, it is not clear that the resulting electrophysiologic changes are the sole mechanisms of clinical anesthetic action. Cells respond to environmental changes in several ways, including alterations in DNA transcription leading to changes in the cell's proteins. We sought to expose the changes in global genomic expression, seeking potential targets involved in the processes of anesthetic-induced amnesia, and persistent long-term side effects of general anesthesia, including nausea and postoperative cognitive decline. Using Affymetrix GeneChips, we surveyed changes in expression across the entire expressed genome of Sprague-Dawley rat (n = 10 baseline, n = 6 isoflurane) basolateral amygdala 6 h after exposure to 15 min of 2% (1.4 MAC) isoflurane. Isoflurane administration was associated with altered expression in 269 unique genes possessing functional annotation. Affected genes were related to DNA transcription, protein synthesis, metabolism, signaling cascades, cytoskeletal structural proteins, and neural-specific proteins, among others. Even brief exposure to isoflurane leads to widespread changes in the genetic control in the amygdala 6 h after exposure. Gene expression is a dynamic process that may explain some long-term effects of anesthesia and that has the potential to modulate some of those effects using specific molecular therapeutics.

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Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999