IL-17A promotes the neuroinflammation and cognitive function in sevoflurane anesthetized aged rats via activation of NF-κB signaling pathway

Abstract

BackgroundTo investigate the role of IL-17A in the neuroinflammation and cognitive function of aged rats anaesthetized with sevoflurane through NF-κB pathway.MethodThe aged and young adult rats were randomly divided into Control (inhale oxygen only), Sevoflurane (inhale oxygen and sevoflurane), Sevo (Sevoflurane) + anti-IL-17A (injected with IL-17A antibody, inhale oxygen and sevoflurane), and Sevo + NC groups (injected with IgG2a antibody, inhale oxygen and sevoflurane). Cognitive function was evaluated by Morris water maze and contextual fear conditioning tests. Tumor necrosis factor (TNF)-α, Interleukin (IL)-1β, IL-6 and monocyte chemoattractant protein (MCP)-1 expressions in the hippocampus of rats were detected by ELISA (enzyme-linked immunosorbent assay) assay, and Nuclear factor (NF)-κB pathway-related proteins by Western blot.ResultsSevoflurane anaesthetized aged rats showed longer escape latency and swimming distance, fewer platform crossing times, shortened stay time in the platform quadrant compared to Control rats; In addition, increased levels in hippocampal expression of malondialdehyde (MDA), IL-17A, NF-κB p65, inducible nitric oxide synthase (iNOS) and COX-2, as well as a reduced level of superoxide dismutase (SOD) were also observed in these animals. However, the sevoflurane anesthetized aged rats treated with anti-IL-17A presented a completely opposite tendency concerning the above factors (all P < 0.05). Nevertheless, there was no significant difference in the acquisition of learning or memory, neuroinflammation and oxidative stress of young adult rats in all groups (all P > 0.05).ConclusionAnti-IL-17A may alleviate neuroinflammation and oxidative stress via inhibiting NF-κB pathway, thereby attenuating post-operative cognitive dysfunction (POCD) in aged rats anaesthetized with sevoflurane.

Cistanches alleviates sevoflurane‐induced cognitive dysfunction by regulating PPAR‐γ‐dependent antioxidant and anti‐inflammatory in rats

“…4,5 Although surgery-induced inflammation or oxidative stress can cause neuroinflammation and damage in the brain and ultimately contribute to cognitive disorder, recent reports suggest that anaesthetic agents used during the surgery are also capable of triggering cognitive impairment. 3,6,7 Sevoflurane is commonly used in clinical anaesthesia for patients of all ages due to its low blood-gas partition coefficient and low metabolic breakdown. 8 However, several lines of evidence have shown that sevoflurane could lead to neuroinflammation and impair cognitive function.…”

“…It is well recognized that neuroinflammation and oxidative stress in the brain play crucial role in the initiation and progress of POCD . Although surgery‐induced inflammation or oxidative stress can cause neuroinflammation and damage in the brain and ultimately contribute to cognitive disorder, recent reports suggest that anaesthetic agents used during the surgery are also capable of triggering cognitive impairment …”

Effect of dexmedetomidine combined with etomidate on IL‑17A and S‑100&beta; expression levels in rats with postoperative cognitive dysfunction

“…Furthermore, as IL-17A may be involved in the process of brain injury (29) and S-100β can be used to evaluate the degree of brain injury (11), the expression levels of IL-17A and S-100β in each group were compared in the present study. The results revealed that the expression levels of IL-17A and S-100β in aged rats with POCD increased, but decreased after drug treatment.…”

“…The IL-17A and S-100β expression levels in the Dex-Eto group were the lowest, indicating that the inhibition effect of dexmedetomidine combined with etomidate on IL-17A and S-100β was the most obvious. Yang et al (29) reported that anti-IL-17A treatment could improve neuroinflammation and oxidative stress, thereby relieving cognitive dysfunction in aged rats, and it was also believed that this mechanism was involved in the reduction of NF-κB pathway. On this basis, the expression of NF-κB p65 in the hippocampus of each group was studied, and the results indicated that the expression of NF-κB p65 was increased in the hippocampus of aged rats with POCD in Morris water maze test, but decreased after drug treatment, with that of the Dex-Eto group being the lowest.…”

Compound Porcine Cerebroside and Ganglioside Injection (CPCGI) Attenuates Sevoflurane-Induced Nerve Cell Injury by Regulating the Phosphorylation of p38 MAP Kinase (p38MAPK)/Nuclear Factor kappa B (NF-κB) Pathway

“…Cell apoptosis, also referred to as programmed cell death, can prevent dysfunctional cells from disturbing the balance of normal tissues, but abnormal apoptosis can lead to cell damage or death [15]. Multiple reports have shown that sevoflurane can accelerate the activation of cysteine aspartate-specific protease (caspase) and apoptosis signaling pathway [16]. Phosphorylation of p38 MAP kinase (p38MAPK) and nuclear translocation of NF-kB p65 are both involved in the signaling pathway, playing a vital role in cell growth and apoptosis [17].…”