Abstract
Several studies have demonstrated that neuroinflammation is the key to perioperative neurocognitive disorders (PND); however, the specific mechanism postsurgery and anesthesia has not yet been fully clarified. The present study is aimed at exploring the effects of P2X4/NLRP3 signaling pathway in neuroinflammation and cognitive impairment after surgery. 12–14-month-old male C57BL/6 mice undergoing open tibial fracture surgery by sevoflurane anesthesia were administered P2X4R inhibitor 5-BDBD or saline was intraperitoneally for 3 consecutive days after surgery. Then, the animals were subjected to Morris water maze test or sacrificed to collect the hippocampus. The level of P2X4R and NLRP3 was estimated by Western blot, the activation of microglia was detected via immunohistochemistry, and the expression of TNF-α, IL-1β, and IL-6 was quantified by enzyme-linked immunosorbent assay. These results indicated that tibial surgery caused cognitive impairment, increased the expression of P2X4R and NLRP3, and aggravated the neuroinflammation and microglia activation. However, intraperitoneal injection of 5-BDBD attenuated these effects. In conclusion, these findings indicated that the P2X4/NLRP3 pathway might be involved in the pathophysiology of PND.
Highlights
Perioperative neurocognitive disorder (PND) is a common complication after surgery, manifested as perioperative memory, attention, executive ability, language ability, and other cognitive function decline [1]
The current study demonstrated that cognitive dysfunction and neuroinflammation after tibial surgery in aged mice were accompanied by an excessive expression of P2X4 receptor
We speculated that P2X4 receptor might be involved in the pathophysiology of PND caused by tibial surgery
Summary
Perioperative neurocognitive disorder (PND) is a common complication after surgery, manifested as perioperative memory, attention, executive ability, language ability, and other cognitive function decline [1]. It delays the patient’s recovery process and prolongs the hospital stay and increases the economic burden on patients and society [2]. Previous studies have shown that purinergic ionotropic (P2X) receptors are closely related to neuroinflammation [4]. Some studies found that the upregulated P2X4 receptor activates microglial cells, producing a variety of proinflammatory cytokines and promoting neuroinflammation, eventually inducing neurotoxicity and damage to neuronal cells [8].
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