NF-κB/P65 signaling pathway: a potential therapeutic target in postoperative cognitive dysfunction after sevoflurane anesthesia.
This study aimed to explore the role of NF-κB/P65 signaling pathway in postoperative cognitive dysfunction (POCD) after sevoflurane anesthesia.



A total of 120 male Sprague-Dawley (SD) rats were selected and assigned into five groups (24 rats in each group): the control, sevoflurane, sevoflurane + splenectomy, pyrrolidine dithiocarbamate (PDTC, a specific inhibitor of NF-κB), and sevoflurane + splenectomy + PDTC groups. Electrocardiogram (ECoG) and behavior changes of rats were monitored before and after anesthesia/operation. Ionized calcium-binding adapter molecules 1 (Iba-1) in the hippocampal zones were observed by immunofluorescence staining. Blood-brain barrier (BBB) permeability was determined by immunohistochemistry. The mRNA and protein expressions of NF-κB/P65 signaling pathway-related proteins and inflammatory cytokines were detected by qRT-PCR assay and Western blotting.



During the anesthesia/operation, the vital signs of rats were stable, but the ECoG in the sevoflurane and sevoflurane + splenectomy groups mainly presented slow waves. The ECoG arousal response in the sevoflurane + splenectomy + PDTC group was observed. At 24 h after the anesthesia/operation, the expressions of NF-κB and P65 in the hippocampal zone, the expressions of IκBα and inflammatory cytokines (IL-1β, IL-6 and TNF-α), the expression of Iba-1 in rat hippocampal dentate gyrus (DG) zone and CA3 zone, and the permeability of BBB were significantly increased and the behavior of rats changed dramatically (all p < 0.05), while PDTC treatments could eliminate these changes induced by the anesthesia/operation (all p < 0.05). No changes were observed in the expressions of NF-κB, P65, IκBα, Iba-1 and inflammatory cytokines (IL-1β, IL-6 and TNF-α), and the permeability of BBB and the behavior of rats in the sevoflurane and the PDTC groups (all p > 0.05).



These results suggest that the inhibition of NF-κB/P65 signaling pathway may relieve POCD after sevoflurane anesthesia.
Department of Anesthesiology, Ningbo No. 2 Hospital, Ningbo, China. junpingche@163.com.
J-W
JW
Zheng
B
B
Meng
X-Y
XY
Li
B
B
Lu
G-R
GR
Wu
J-P
JP
Chen
D018685:Anesthetics, Inhalation / Q000009:adverse effects*; D000818:Animals; D001812:Blood-Brain Barrier; D060825:Cognitive Dysfunction / Q000139:chemically induced*; D016207:Cytokines / Q000378:metabolism; D008297:Male; D008738:Methyl Ethers / Q000009:adverse effects*; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077149:Sevoflurane; D015398:Signal Transduction; D013859:Thiocarbamates / Q000494:pharmacology; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D018685:Anesthetics, Inhalation; D016207:Cytokines; D008738:Methyl Ethers; D011759:Pyrrolidines; C498145:Rela protein, rat; D013859:Thiocarbamates; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; C020972:pyrrolidine dithiocarbamic acid; D000077149:Sevoflurane