• J F Perez-Zoghbi, W Zhu, M R Grafe, and A M Brambrink.
• Department of Anesthesiology, Columbia University, College of Physicians & Surgeons, NewYork-Presbyterian Hospital, New York, NY, USA.
• Br J Anaesth. 2017 Sep 1; 119 (3): 506-516.

BackgroundExposure of infant animals to clinically used anaesthetics is associated with acute structural brain abnormalities and development functional alterations. The α 2 -adrenoceptor agonist dexmedetomidine (DEX) induces sedation, analgesia, and provides neuroprotection in experimental brain injury models. However, it is unknown whether DEX also affords protection in the developing brain against anaesthesia using sevoflurane (SEVO), which is commonly used in paediatric anaesthesia.MethodsInfant rats were exposed on postnatal day seven for six h to 2.5% SEVO and were given i.p. injections of saline or DEX (1-50 µg kg -1 ) three times during the exposure. Level of anaesthesia, respiratory rates, and arterial blood gasses were assessed for each animal. Apoptosis was determined in brain slices immunostained for activated caspase-3 (AC-3) using a computerised approach.ResultsSEVO alone induced a surgical plane of anaesthesia, and all animals survived the study. SEVO induced an approximately 10-fold increase in AC-3 positive cells in several cortical and subcortical brain regions compared with untreated control animals. Co-administration of DEX 1 µg kg -1 with SEVO significantly reduced apoptosis in all brain areas, affording the highest protection in the thalamus (84% reduction) and lowest in the hippocampus and cortical areas (∼50% reduction). DEX 5-25 µg kg -1 plus SEVO dose-dependently increased infant rat mortality.ConclusionsSEVO anaesthesia induced widespread apoptosis in infant rat brain. Co-administration of DEX (1 µg kg -1 ) provided significant protection, whereas DEX (5 µg kg -1 or higher) plus SEVO increased mortality. Our findings suggest that DEX could be an attractive therapeutic for future studies investigating its neuroprotective potential in a translational animal model.© The Author 2017. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com

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