Abstract
Postoperative cognitive dysfunction (POCD) is a common postoperative central nervous system complication, especially in the elderly. It has been consistently reported that the pathological process of this clinical syndrome is related to neuroinflammation and microglial proliferation. Glycogen synthase kinase 3β (GSK-3β) is a widely expressed kinase with distinct functions in different types of cells. The role of GSK-3β in regulating innate immune activation has been well documented, but as far as we know, its role in POCD has not been fully elucidated. Lithium chloride (LiCl) is a widely used inhibitor of GSK-3β, and it is also the main drug for the treatment of bipolar disorder. Prophylactic administration of lithium chloride (2 mM/kg) can inhibit the expression of proinflammatory mediators in the hippocampus, reduce the hippocampal expression of NF-κB, and increase both the downregulation of M1 microglial-related genes (inducible nitric oxide synthase and CD86) and upregulation of M2 microglial-related genes (IL-10 and CD206), to alleviate the cognitive impairment caused by orthopedic surgery. In vitro, LiCl reversed LPS-induced production of proinflammatory mediators and M1 polarization of microglia. To sum up these results, GSK-3β is a key contributor to POCD and a potential target of neuroprotective strategies.
Highlights
Postoperative cognitive dysfunction (POCD), a common postoperative complication, which is usually observed in elderly patients, refers to cognitive decline after surgery
Tibial surgery impairs the cognitive function of aged rats, and Glycogen synthase kinase 3β (GSK-3β) inhibition limits the adverse cognitive outcomes caused by tibial surgery
Pretreatment with LiCl remarkably reduced the number of migration cells when compared with control group (Figure 5(b)). These results suggest that GSK-3β may lead to recruitment of microglial cells
Summary
POCD, a common postoperative complication, which is usually observed in elderly patients, refers to cognitive decline after surgery. For the past few years, the incidence and even mortality of POCD have been increasing. Severe surgical trauma and advanced age are the two main risk factors for POCD [2]. The pathogenesis of POCD is not clear, there is growing evidence that neuroinflammation plays a crucial part in the disease [3]. Peripheral surgical trauma can bring about hippocampal-dependent learning and memory impairment, which are relevant to the increased level of IL1β in the hippocampus [4]. The strategy of inhibiting hippocampal inflammation by blocking TNF-α can in turn prevent cognitive decline in aseptic surgical rat models [5]
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