Icariin reduces cognitive dysfunction induced by surgical trauma in aged rats by inhibiting hippocampal neuroinflammation

Abstract

Postoperative cognitive dysfunction (POCD) is a common postsurgical complication in elderly individuals, significantly impacting the quality of life of patients; however, there is currently no effective clinical treatment for POCD. Recent studies have shown that Icariin (ICA) has antiaging effects and improves cognitive function, but its effect in POCD has not been studied. In this study, we investigated the influence of ICA on cognitive function and the TLR4/NF-κB signaling pathway in a POCD rat model. We found that ICA reduced surgery-induced memory impairment, decreased hippocampal inflammatory responses, ameliorated neuronal injury in the hippocampus and inhibited microglial activation. In addition, we also observed that ICA inhibited activation of the TLR4/NF-κB signaling pathway. In summary, our research suggest that ICA can ameliorate surgery-induced memory impairment and that the improvements resulting from administration of ICA may be associated with inhibition of hippocampal neuroinflammation. Our research findings also provide insight into potential therapeutic targets and methods for POCD.

GLUT1-mediated microglial proinflammatory activation contributes to the development of stress-induced spatial learning and memory dysfunction in mice

“…Numerous clinical and preclinical studies have confirmed a strong correlation between neuroinflammation and cognitive disorders, including Alzheimer’s disease and stress-related cognitive impairment [ 35 , 36 ]. Therapies targeting neuroinflammation have also shown promising results in alleviating cognitive dysfunctions [ 37 , 38 ]. Microglia are emerging as critical key regulators of the inflammatory response process in the central nervous system; overactivation of these cells might impair cognition through the excessive release of inflammatory cytokines [ 9 ].…”

Surgery induces neurocognitive disorder via neuroinflammation and glymphatic dysfunction in middle-aged mice with brain lymphatic drainage impairment

“…Subsequently, a later study established a causal relationship between HMGB1 and PND by reporting that inhibition of HMGB1 via its neutralizing antibody effectively mitigated PND in aged rats undergoing partial hepatolobectomy (Terrando et al, 2016). Several drugs exert their pharmacological effects through the inhibition of various molecules within the HMGB1/TLR4/NF-κB pathway, resulting in reduced hippocampal inflammatory responses, suppressed microglial activation, mitigated neuronal injury and attenuated surgery-induced memory impairment (Wang et al, 2022(Wang et al, , 2023Yao et al, 2023). As for the glymphatic system, there are limited studies associated with this pathway.…”

Microglial exosome miR‐124‐3p in hippocampus alleviates cognitive impairment induced by postoperative pain in elderly mice

“…Surgical trauma induces the release of pro‐inflammatory cytokines and chemokines at the site of tissue injury, initiating a local inflammatory response. These inflammatory mediators can activate peripheral immune cells, such as macrophages and monocytes, which then infiltrate the CNS and further contribute to the neuroinflammatory cascade 10,11 . In the hippocampus, microglia, the resident immune cells of the brain, play a key role in sensing and responding to these inflammatory signals 12 .…”

“…These inflammatory mediators can activate peripheral immune cells, such as macrophages and monocytes, which then infiltrate the CNS and further contribute to the neuroinflammatory cascade. 10 , 11 In the hippocampus, microglia, the resident immune cells of the brain, play a key role in sensing and responding to these inflammatory signals. 12 Microglia activation is a complex process involving the transformation of microglia into an activated phenotype, characterized by morphological changes and the release of pro‐inflammatory cytokines, such as tumour necrosis factor α (TNF‐α) and interleukin‐1β (IL‐1β).…”