Galectin‐1 ameliorates perioperative neurocognitive disorders in aged mice

Abstract

Introduction The incidence of perioperative neurocognitive disorders (PND) is higher in the elderly patients undergoing surgery. Microglia activation‐mediated neuroinflammation is one of the hallmarks of PND. Galectin‐1 has been identified as a pivotal modulator in the central nervous system (CNS), while the role of galectin‐1 in PND induced by microglia‐mediated neuroinflammation is still undetermined. Methods An exploratory laparotomy model anesthetized with isoflurane was employed to investigate the role of galectin‐1 on PND in aged mice. Open field test and Morris water maze were used to test the cognitive function 3‐ or 7‐days post‐surgery. The activation of microglia in the hippocampus of aged mice was tested by immunohistochemistry. Western blot, enzyme‐linked immunosorbent assay (ELISA), and quantitative real‐time polymerase chain reaction (qRT‐PCR) were employed to elucidate the underlying mechanisms. Results Galectin‐1 attenuated the cognitive dysfunction induced by surgery in aged mice and inhibited microglial activity. Moreover, galectin‐1 decreased the expression level of inflammatory proteins (interleukin‐1β, interleukin‐6, and tumor necrosis factor‐α), and prevented neuronal loss in the hippocampus. Galectin‐1 inhibited the inflammation of BV2 microglial cells induced by lipopolysaccharide via decreasing the translocation of NF‐κB p65 and c‐Jun, while this kind of inhibition was rescued when overexpressing IRAK1. Conclusion Our findings provide evidence that galectin‐1 may inhibit IRAK1 expression, thus suppressing inflammatory response, inhibiting neuroinflammation, and improving ensuing cognitive dysfunction. Collectively, these findings unveil that galectin‐1 may elicit protective effects on surgery‐induced neuroinflammation and neurocognitive disorders.

Electroacupuncture ameliorates postoperative cognitive dysfunction and associated neuroinflammation via NLRP3 signal inhibition in aged mice

“… 5 , 6 Surgery activates an immune response and results in the release of systemic proinflammatory factors and eventually leads to neuroinflammation. 7 , 8 , 9 Studies have shown that microglia are activated by peripheral proinflammatory cytokines 10 and can release additional proinflammatory cytokines, exacerbating neuroinflammation and brain damage. 11 Once activated by proinflammatory cytokines in the brain, microglia tend to separate into two “polarizing” phenotypes M1 and M2, sometimes associated with the release of cytokines.…”

Cellular Phenotypic Transformation in Heart Failure Caused by Coronary Heart Disease and Dilated Cardiomyopathy: Delineating at Single-Cell Level

“…Pathway enrichment showed that EC1 was highly expressed in inflammation-related pathways, such as GO-POSITIVE-REGULATION-OF-TNF-MEDIATED-SIGNALING-PATHWAY and GO-REGULATION-OF-MONOCYTE-CHEMOTAXIS ( Supplementary Figure S3 C). At the transcriptional level, EC1 was also found to highly expressed inflammatory TFs such as Jun and Fos [ 21 , 22 ] ( Supplementary Figure S3 D). The diverse functional involvement of ECs prompted us to explore cell–cell communications of EC1, the crosstalk showed that EC1 could interact with other cells through many chemokines and receptors ( Supplementary Figure S3 E).…”

mTOR‐mediated autophagy in the hippocampus is involved in perioperative neurocognitive disorders in diabetic rats

“…PND are common neurological complications that include postoperative delirium (POD), postoperative cognitive decline (POCD), and delayed neurocognitive recovery and occur in 10% to 54% of patients after surgery. 2 Although advanced age, neuroinflammation, and cerebrovascular dysfunction are thought to be important factors for cognitive impairment in the pathogenesis of neurodegenerative disorders, [38][39][40][41] the exact mechanisms underlying the pathogenesis of PND remain largely unclear. Recently, several clinical studies have indicated that diabetes and acute perioperative hyperglycemia are independent risk factors in the development of PND.…”