Activation of the canonical nuclear factor-κB pathway is involved in isoflurane-induced hippocampal interleukin-1β elevation and the resultant cognitive deficits in aged rats.
Although much recent evidence has demonstrated that neuroinflammation contributes to volatile anesthetic-induced cognitive deficits, there are few existing mechanistic explanations for this inflammatory process. This study was conducted to investigate the effects of the volatile anesthetic isoflurane on canonical nuclear factor (NF)-κB signaling, and to explore its association with hippocampal interleukin (IL)-1β levels and anesthetic-related cognitive changes in aged rats. After a 4-h exposure to 1.5% isoflurane in 20-month-old rats, increases in IκB kinase and IκB phosphorylation, as well as a reduction in the NF-κB inhibitory protein (IκBα), were observed in the hippocampi of isoflurane-exposed rats compared with control rats. These events were accompanied by an increase in NF-κB p65 nuclear translocation at 6h after isoflurane exposure and hippocampal IL-1β elevation from 1 to 6h after isoflurane exposure. Nevertheless, no significant neuroglia activation was observed. Pharmacological inhibition of NF-κB activation by pyrrolidine dithiocarbamate markedly suppressed the IL-1β increase and NF-κB signaling, and also mitigated the severity of cognitive deficits in the Morris water maze task. Overall, our results demonstrate that isoflurane-induced cognitive deficits may stem from upregulation of hippocampal IL-1β, partially via activation of the canonical NF-κB pathway, in aged rats.
Department of Anesthesiology, Peking University Third Hospital, Beijing 100191, China.
Zheng-Qian
ZQ
Li
Xiao-Ying
XY
Rong
Ya-Jie
YJ
Liu
Cheng
C
Ni
Xiao-Sheng
XS
Tian
Na
N
Mo
De-Hua
DH
Chui
Xiang-Yang
XY
Guo
D000375:Aging; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D003071:Cognition / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology*; D007530:Isoflurane / Q000494:pharmacology*; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000276:immunology*; D009457:Neuroglia / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D013859:Thiocarbamates / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
D018685:Anesthetics, Inhalation; D053583:Interleukin-1beta; D016328:NF-kappa B; D011759:Pyrrolidines; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid; D007530:Isoflurane
Interleukin-1β; Isoflurane; NF-κB; Postoperative cognitive dysfunction