Beneficial Effects of Remifentanil Against Excitotoxic Brain Damage in Newborn Mice

Abstract

Background: Remifentanil, a synthetic opioid used for analgesia during cesarean sections, has been shown in ex vivo 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 in vivo model of excitotoxic neonatal brain injury. Methods: 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, in situ 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. Results: 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. Conclusions: In vivo 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.

Remifentanil up‐regulates HIF1α expression to ameliorate hepatic ischaemia/reperfusion injury via the ZEB1/LIF axis

“…with remifentanil (30 μg/kg in total; 091110, Yichang Renfu Pharmaceutical Industry) 3 times, and were then injected (i.p.) twice with 1 μL of lentivirus at a concentration of 5 × 10 8 TU/mL each time 33‐35 . Animal use and experimental procedures were carried out in a protocol approved by the Experimental Animal Ethics Committee of Xi'an Jiaotong University.…”

Remifentanil Protects against Lipopolysaccharide-Induced Inflammation through PARP-1/NF-κB Signaling Pathway

“…Treatment with remifentanil influences neutrophil migration through endothelial cell monolayers, as well as adhesion molecule expression [14]. Moreover, remifentanil is proved to exert protective effect in a variety of diseases, such as acute lung injury, ischemia/reperfusion injury, and excitotoxic brain damage [5,15,16]. However, the potential role and mechanism of remifentanil in sepsis has not been yet fully investigated.…”

Efficacy and Safety Aspects of Remifentanil Sedation for Intubation in Neonates: A Retrospective Study

“…Further research is needed to establish safety profiles for the use of ketamine in neonates due to concerns regarding possible neurotoxicity in animal studies (22). Regarding remifentanil, studies performed in mice have shown that it has an antiapoptotic impact and that it exerts beneficial effects against excitotoxicity on the developing mouse brain that is associated with a reduction in the brain lesion size as well as prevention of a number of behavioral deficits in young mice (23, 24). It should be noted that the neurotoxicity of some anesthetic agents has mainly been demonstrated in animals, and most of the time in the absence of painful procedures.…”