Adiponectin attenuates splenectomy-induced cognitive deficits by alleviating neuroinflammation and oxidative stress via the TLR4/MyD88/NF-κb signaling pathway in aged rats

Background: Perioperative neurocognitive disorder (PND) is a common adverse event after surgical trauma in elderly patients. The pathogenesis of PND is still unclear. Adiponectin (APN) is a plasma protein secreted by adipose tissue. We have reported that decreased APN expression is associated with PND patients. APN may be a promising therapeutic agent for PND. However, the neuroprotective mechanism of APN in PND is still unclear. Methods Eighteen month-old male Sprague Dawley rats were assigned to six groups: the sham, sham + APN (intragastric (i.g.) administration of 10 µg/kg/day for 20 days before splenectomy), PND (splenectomy), PND + APN, PND + TAK-242 (intraperitoneal (i.p.) administration of 3 mg/kg TAK-242) and PND + APN + LPS (i.p. administration of 2 mg/kg LPS). The cognitive function of the rats was assessed with the Morris water maze (MWM) test. Immunohistochemistry/ immunofluorescence, western blotting and ELISA were used to evaluate the activation of the TLR4/NF-κb axis, oxidative stress-mediated apoptosis, microglial activation and proinflammatory cytokine expression in the hippocampus. Results We first found that APN treatment significantly improved learning and cognitive function in the MWM test after surgical trauma. Further experiments showed that APN could inhibit the TLR4/MyD88/NF-κb p65 pathway to decrease the degree of oxidative damage (MDA, SOD and caspase 3) and microglia-mediated neuroinflammation (IBA1, TNF-α, IL-1β and IL-6). The TLR4 antagonist TAK-242 had a similar effect as APN, while the TLR4 agonist LPS abolished the beneficial effect of APN. Conclusions APN exerts a neuroprotective effect against cognitive deficits induced by peripheral trauma, and the possible mechanisms include inhibition of oxidative stress and neuroinflammation, which is mediated by suppression of the TLR4/MyD88/NF-κb signaling pathway. We propose that APN is a promising candidate for PND treatment.