PMID- 33103411 OWN - NLM STAT- MEDLINE DCOM- 20210114 LR - 20210114 IS - 0393-974X (Print) IS - 0393-974X (Linking) VI - 34 IP - 5 DP - 2020 Sep-Oct, TI - Remifentanil protects neurological function of rats with cerebral ischemia-reperfusion injury via NR2B/CaMKIIalpha signaling pathway. PG - 1647-1656 LID - 10.23812/20-169-A [doi] AB - The effects of remifentanil were studied on cerebral ischemia-reperfusion injury (IRI) in rats, and its regulatory effect was explored on the N-methyl D-aspartate receptor subtype 2B (NR2B)/calcium/calmodulin-dependent protein kinase type II subunit alpha (CaMKII) signaling pathway in cerebral tissues. A total of 40 Sprague-Dawley rats were randomly assigned into sham group, model group, low-dose group (remifentanil injected into the caudal veins at 2 mug/kg) and high-dose group (remifentanil injected into the caudal veins at 10 mug/kg). Then, in the model, low-dose and high-dose groups, the rat model of cerebral IRI was established through middle cerebral artery occlusion (namely, ischemia for 1 h and reperfusion for 2 h), while no thread was inserted into the rats in the sham group. Neurological function of rats in each group was evaluated, and the cerebral infarct size was measured using 2,3,5-triphenyltetrazolium chloride (TTC) staining. Moreover, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining was performed to determine the neuronal apoptosis level, and mitochondrial membrane potential was measured via JC-1 assay. Moreover, the reactive oxygen species (ROS) level in neurons and the malondialdehyde (MDA) content in cerebral tissues were determined using 2',7'-dichlorofluorescin diacetate (DCFH-DA) assay and enzyme-linked immunosorbent assay (ELISA), respectively. Finally, the expression levels of apoptosis-associated proteins and the NR2B/CaMKIIalpha signaling pathway-associated proteins in cerebral tissues were measured by Western blotting. Remifentanil preconditioning substantially decreased the neurological score of rats (p<0.01), cerebral infarct size (p<0.01), neuronal apoptosis level (p<0.01), ROS level in neurons (p<0.01), MDA content (p<0.01) and expression levels of cysteinyl aspartate specific proteinase-3 (Caspase-3), NR2B, phosphorylated CaMKIIalpha (p-CaMKIIalpha) and p-cAMP responsive element binding protein (p-CREB) (p<0.01), but it increased the mitochondrial membrane potential (p<0.01) and B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X protein (Bax) ratio (p<0.01). Remifentanil can repress the NR2B/ CaMKIIalpha signaling pathway in the neurons of rats with cerebral IRI to decrease the p-CREB expression, ROS level and MDA content in neurons, neuronal apoptosis level and cerebral infarct size, and increase the mitochondrial membrane potential, thereby protecting the neurological function. CI - Copyright 2020 Biolife Sas. www.biolifesas.org. FAU - Chen, C R AU - Chen CR AD - Department of Anesthesiology, Xingtai People's Hospital, Xingtai, China. FAU - Bi, H L AU - Bi HL AD - Department of Operation room, Affiliated Jinxiang Hospital of Jining Medical University, Jining, China. FAU - Li, X AU - Li X AD - Department of Anesthesiology, Affiliated Jinxiang Hospital of Jining Medical University, Jining, China. FAU - Li, Z M AU - Li ZM AD - Department of Health Management, The PLA Rocket Force Characteristic Medical Center, Beijing, China. LA - eng PT - Journal Article PL - Italy TA - J Biol Regul Homeost Agents JT - Journal of biological regulators and homeostatic agents JID - 8809253 RN - 0 (NR2B NMDA receptor) RN - 0 (Receptors, N-Methyl-D-Aspartate) RN - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Type 2) RN - EC 2.7.11.17 (Camk2a protein, rat) RN - P10582JYYK (Remifentanil) SB - IM MH - Animals MH - Apoptosis MH - Calcium-Calmodulin-Dependent Protein Kinase Type 2 MH - Rats MH - Rats, Sprague-Dawley MH - Receptors, N-Methyl-D-Aspartate MH - Remifentanil/pharmacology MH - *Reperfusion Injury/prevention & control MH - Signal Transduction OTO - NOTNLM OT - Aremifentanil OT - NR2B/CaMKIIa signaling pathway OT - apoptosis OT - cerebral ischemia-reperfusion injury OT - rats EDAT- 2020/10/27 06:00 MHDA- 2021/01/15 06:00 CRDT- 2020/10/26 08:02 PHST- 2020/10/26 08:02 [entrez] PHST- 2020/10/27 06:00 [pubmed] PHST- 2021/01/15 06:00 [medline] AID - 12 [pii] AID - 10.23812/20-169-A [doi] PST - ppublish SO - J Biol Regul Homeost Agents. 2020 Sep-Oct,;34(5):1647-1656. doi: 10.23812/20-169-A.