AUTHOR=Chollat Clément , Lecointre Maryline , Leuillier Matthieu , Remy-Jouet Isabelle , Do Rego Jean-Claude , Abily-Donval Lénaïg , Ramdani Yasmina , Richard Vincent , Compagnon Patricia , Dureuil Bertrand , Marret Stéphane , Gonzalez Bruno José , Jégou Sylvie , Tourrel Fabien 

TITLE=Beneficial Effects of Remifentanil Against Excitotoxic Brain Damage in Newborn Mice

JOURNAL=Frontiers in Neurology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2019.00407

DOI=10.3389/fneur.2019.00407

ISSN=1664-2295

ABSTRACT=<p><bold>Background:</bold> Remifentanil, a synthetic opioid used for analgesia during cesarean sections, has been shown in <italic>ex vivo</italic> experiments to exert anti-apoptotic activity on immature mice brains. The present study aimed to characterize the impact of remifentanil on brain lesions using an <italic>in vivo</italic> model of excitotoxic neonatal brain injury.</p><p><bold>Methods:</bold> Postnatal day 2 (P2) mice received three intraperitoneal injections of remifentanil (500 ng/g over a 10-min period) or saline just before an intracortical injection of ibotenate (10 μg). Cerebral reactive oxygen species (ROS) production, cell death, <italic>in situ</italic> labeling of cortical caspase activity, astrogliosis, inflammation mediators, and lesion size were determined at various time points after ibotenate injection. Finally, behavioral tests were performed until P18.</p><p><bold>Results:</bold> In the injured neonatal brain, remifentanil significantly decreased ROS production, cortical caspase activity, DNA fragmentation, interleukin-1β levels, and reactive astrogliosis. At P7, the sizes of the ibotenate-induced lesions were significantly reduced by remifentanil treatment. Performance on negative geotaxis (P6-8) and grasping reflex (P10-12) tests was improved in the remifentanil group. At P18, a sex specificity was noticed; remifentanil-treated females spent more time in the open field center than did the controls, suggesting less anxiety in young female mice.</p><p><bold>Conclusions:</bold><italic>In vivo</italic> exposure to remifentanil exerts a beneficial effect against excitotoxicity on the developing mouse brain, which is associated with a reduction in the size of ibotenate-induced brain lesion as well as prevention of some behavioral deficits in young mice. The long-term effect of neonatal exposure to remifentanil should be investigated.</p>