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Anesth Analg 2006;102:456-461
© 2006 International Anesthesia Research Society
doi: 10.1213/01.ane.0000194301.79118.e9


ANESTHETIC PHARMACOLOGY

The Effects of Dexmedetomidine on Perinatal Excitotoxic Brain Injury are Mediated by the {alpha}2A-Adrenoceptor Subtype

Andrea Paris, MD*, Jean Mantz, MD, PhD§, Peter H. Tonner, MD*, Lutz Hein, MD{dagger}, Marc Brede, MD{ddagger}, and Pierre Gressens, MD, PhD||

*Department of Anaesthesiology and Intensive Care Medicine, University Hospital Schleswig-Holstein, Campus Kiel; {dagger}Institute of Experimental and Clinical Pharmacology and Toxicology, University of Freiburg; {ddagger}Department of Anaesthesia and Critical Care, University of Wuerzburg Hospitals, Germany; §Hôpital Beaujon, Assistance Publique des Hôpitaux de Paris; and ||INSERM U 676 & Service de Neuropédiatrie, Hôpital Robert Debré, Paris, France

Address correspondence to Andrea Paris, MD, Department of Anaesthesiology and Intensive Care Medicine, University Hospital Schleswig-Holstein, Campus Kiel, Schwanenweg 21, D-24105 Kiel, Germany. Address e-mail to paris{at}anaesthesie.uni-kiel.de.

We performed the current study in mice lacking individual {alpha}2-adrenoceptor subtypes to elucidate the contribution of {alpha}2-adrenoceptor subtypes to the neuroprotective properties of dexmedetomidine in a model of perinatal excitotoxic brain injury. On postnatal Day 5, wild-type mice and mice lacking {alpha}2A-adrenoceptor ({alpha}2A-KO) or {alpha}2C-adrenoceptor subtypes ({alpha}2C-KO) were randomly assigned to receive dexmedetomidine (3 µg/kg) or phosphate-buffered saline intraperitoneally. Thirty minutes after the intraperitoneal injection, the glutamatergic agonist ibotenate (10 µg) was intracerebrally injected, producing transcortical necrosis and white matter lesions that mimic perinatal human hypoxic-like lesions. Quantification of the lesions was performed on postnatal Day 10 by histopathologic examination. Dexmedetomidine reduced mean lesion size in the cortex of wild-type mice and {alpha}2C-KO mice by 44% and 49%, respectively. Ibotenate-induced white matter lesions were reduced by 71% (wild-type mice) and 75% ({alpha}2C-KO mice) after pretreatment with dexmedetomidine. In contrast, in {alpha}2A-KO mice, dexmedetomidine did not protect against the cortical excitotoxic insult, and white matter lesions were even more pronounced (82% increase of mean lesion size). Dexmedetomidine provides potent neuroprotection in a model of perinatal excitotoxic brain damage. This effect was completely abolished in {alpha}2A-KO mice, suggesting that the neuroprotective effect is mediated via the {alpha}2A-adrenoceptor subtype.




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Lippincott, Williams & Wilkins 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 HighWire Press
Copyright © 2006 by the International Anesthesia Research Society.