Journal Article Journal Article Ppublish 4 citations
PubMed: 35758051 DOI: 10.1080/21655979.2022.2090608
IL-17A deletion reduces sevoflurane-induced neurocognitive impairment in neonatal mice by inhibiting NF-κB signaling pathway.
Bioengineered 13(6):14562-14577
Authors: Qi Zhang, Yanan Li, Chunping Yin, Mingyang Gao, Jiaxu Yu, Junfei Guo, Xiaohui Xian, Zhiyong Hou, Qiujun Wang
Affiliations
- Department of Anesthesiology, Hebei Children's Hospital Affiliated to Hebei Medical University, Shijiazhuang, Hebei, China. Department of Anesthesiology, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
- Department of Anesthesiology, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
- Department of Orthopaedics, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
- NHC Key Laboratory of Intelligent Orthopaedic, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
- Department of Pathophysiology, Hebei Medical University, Shijiazhuang, Hebei, China.
- Department of Orthopaedics, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China. NHC Key Laboratory of Intelligent Orthopaedic, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
- Department of Anesthesiology, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
Abstract
We investigated the role of IL-17A in sevoflurane-inducedneurocognitive impairment in neonatal mice. Seventy-two wild-type (WT) and 42 IL-17A knockout (KO) neonatal mice were randomly divided into WT ( = 36), IL-17A ( = 6), sevoflurane (Sev, = 36), and IL-17A + sevoflurane (IL-17A + Sev, = 36) groups. The latter two groups were given 3% sevoflurane for 2 h per day on postnatal days (P) 6-8. Behavioral experiments were performed on P30-36. At P37, RNA sequencing and qRT-PCR of the hippocampus was performed, neurons were detected by Nissl staining, and neuropathological changes were evaluated by HE staining. NF-κB pathway-related proteins were evaluated by western blot and immunofluorescence analyses, IL-1β and IL-6 levels were assessed by ELISA. RNA sequencing identified 131 differentially expressed genes, highlighting several enriched biological processes (chemokine activity, immune response, extracellular region, extracellular space, inflammatory response) and signaling pathways (IL-17 signaling pathway, chemokine signaling pathway, cytokine-cytokine receptor interaction, ECM-receptor interaction and influenza A). Repeated sevoflurane exposures induced long-term cognitive impairment in WT mice. The cognitive impairment was comparatively less severe in IL-17A KO mice. In addition, the increased levels of NF-κB p65, iNOS, COX-2, IL-17A, IL-6 and IL-1β, reduced neuronal numbers and neuropathological changes were ameliorated in neonatal mice in the IL-17A + Sev group compared with neonatal mice in Sev group. IL-17A deletion protects against long-term cognitive impairment induced by repeated sevoflurane exposure in neonatal mice. The underlying mechanism may relate to inhibiting NF-κB signaling pathway as well as the reducing neuroinflammation.
MeSH
Cytokines, Sevoflurane, Bioengineering, Chemokines, Cognitive Dysfunction, Cognition Disorders