Postoperative cognitive dysfunction: an acute approach for the development of novel treatments for neuroinflammation

Granger, Kiri; Barnett, Jennifer H.

doi:10.1016/j.drudis.2021.01.019

Cited by 30 publications

(20 citation statements)

References 34 publications

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“…Postoperative cognitive dysfunction (POCD) is one of the most common postoperative complications in elderly patients ( Granger and Barnett, 2021 ) and is characterized by declines in learning, memory, attention, and executive capability following anesthesia and surgery ( Chen et al, 2019 ; Yan et al, 2020 ). Clinical evidence indicates that POCD may contribute to increased mortality, decreased quality of life, prolonged hospitalization, and increased burden on the medical care system ( Steinmetz et al, 2009 ).…”

Section: Introductionmentioning

confidence: 99%

A Noradrenergic Lesion Attenuates Surgery-Induced Cognitive Impairment in Rats by Suppressing Neuroinflammation

Wang

Zhou

et al. 2021

Front. Mol. Neurosci.

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Postoperative cognitive dysfunction (POCD) is a common postoperative neurocognitive complication in elderly patients. However, the specific pathogenesis is unknown, and it has been demonstrated that neuroinflammation plays a key role in POCD. Recently, increasing evidence has proven that the locus coeruleus noradrenergic (LCNE) system participates in regulating neuroinflammation in some neurodegenerative disorders. We hypothesize that LCNE plays an important role in the neuroinflammation of POCD. In this study, 400 μg of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) was injected intracerebroventricularly into each rat 7 days before anesthesia/surgery to deplete the locus coeruleus (LC) noradrenaline (NE). We applied a simple laparotomy and brief upper mesenteric artery clamping surgery as the rat POCD model. The open field test, novel objection and novel location (NL) recognition, and Morris water maze (MWM) were performed to assess postoperative cognition. High-performance liquid chromatography (HPLC) was used to measure the level of NE in plasma and brain tissues, and immunofluorescence staining was applied to evaluate the activation of microglia and astrocytes. We also used enzyme-linked immune-sorbent assay (ELISA) to assess the levels of inflammatory cytokines and brain-derived neurotrophic factor (BDNF). Pretreatment with DSP-4 decreased the levels of systemic and central NE, increased the level of interleukin-6 (IL-6) in the plasma at 6 h after the surgery, decreased the concentration of IL-6 in the prefrontal cortex and hippocampus, and decreased the level of interleukin-1β (IL-1β) in the plasma, prefrontal cortex, and hippocampus at 1 week postoperatively. In addition, DSP-4 treatment attenuated hippocampal-dependent learning and memory impairment in rats with POCD, with a downregulation of the activation of microglia and astrocytes in the prefrontal cortex and hippocampus. In conclusion, these findings provide evidence of the effects of LCNE in modulating neuroinflammation in rats with POCD and provide a new perspective in the prevention and treatment of POCD.

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Section: Introductionmentioning

confidence: 99%

A Noradrenergic Lesion Attenuates Surgery-Induced Cognitive Impairment in Rats by Suppressing Neuroinflammation

Wang

Zhou

et al. 2021

Front. Mol. Neurosci.

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“…Sustained neuroinflammation is implicated in the progression of cognitive impairment [ 27 ]. Increasing evidence suggests that postoperative trauma causes central and systemic inflammation, resulting in cognitive dysfunction.…”

Section: Discussionmentioning

confidence: 99%

Electroacupuncture Ameliorates Tibial Fracture-Induced Cognitive Dysfunction by Elevating α7nAChR Expression and Suppressing Mast Cell Degranulation in the Hippocampus of Rats

Zhou

Mao

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Intracerebral neuroinflammation, closely related to brain mast cell (MC) activation, performs an integral function in the pathogenic process of postoperative cognitive dysfunction (POCD). In addition to regulating cognitive activities, the alpha-7-nicotinic acetylcholine receptor (α7nAChR) engages in the progression of cognitive deficiency. In this research, we aimed to investigate how electroacupuncture (EA) affects the cognitive function in rats after tibial fracture surgery to determine whether the underlying mechanism involves the inhibition of hippocampal MC degranulation via α7nAChR. A rat model of tibial fracture surgery for inducing POCD was developed and subjected to treatment with EA or the α7nAChR antagonist α-bungarotoxin (α-BGT) and the α7nAChR agonist PHA-543613. The spatial memory tasks in the Morris Water Maze (MWM) test showed that both EA and PHA-543613-treated rats performed significantly better than untreated rats, with reduced escape latency and increased frequency of passage through the platform. However, EA and PHA-543613 intervention decreased the protein and mRNA levels of High-mobility group box-1(HMGB-1) and proinflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) in the serum and hippocampus, respectively, by upregulating α7nAChR in the hippocampus. Furthermore, EA and PHA-543613 pretreatment reduced the number of activated MCs and suppressed neuronal apoptosis after tibial fracture surgery in the hippocampal CA1 regions, which was reversed by α-BGT. The findings indicated that EA pretreatment ameliorated POCD after tibial fracture surgery in rats by inhibiting brain MC activation and neuroinflammation mediated by the α7nAChR-dependent cholinergic anti-inflammatory system.

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“…Peripheral inflammatory factors can cause central nervous system (CNS) inflammatory response through direct or indirect pathways. When excessive CNS inflammatory response occurs, it can affect cognitive function by producing the following effects ( 25 – 30 ). First, inflammatory cytokines affect neural activity and synaptic connections ( 25 ).…”

Section: Discussionmentioning

confidence: 99%

Anesthetic Effect of the Fascia Iliaca Compartment Block with Different Approaches on Total Hip Arthroplasty and Its Effect on Postoperative Cognitive Dysfunction and Inflammation

et al. 2022

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ObjectiveThe objective of this article is to make a comparison of the anesthetic effects of the inside and outside fascia iliaca compartment block (FICB) in total hip arthroplasty (THA) and to study the effect of the different approaches of the FICB on postoperative cognitive dysfunction (POCD) and serum inflammatory cytokines in THA patients.MethodsA total of 60 patients who received THA treatment from January 2021 to December 2021 were divided into two groups, namely, Inside group (inside approach of the FICB) and Outside group (outside approach of the FICB), according to the different approaches of the FICB. Forty-eight hours after surgery, we compared the use of ropacaine dosage, visual analogue scale (VAS) score, the use of patient-controlled analgesia (PCA), mini-mental state examination (MMSE) score, the incidence of POCD, and the serum levels of IL-1, IL-6. Secondary indicators include surgical indicators and the quality of anesthesia cannula.ResultsThe ratio of re-fix the catheter, intubation time, and the use of ropacaine dosage at 48 h after surgery in the Outside group were significantly higher than that in the Inside group (p < 0.05), while the depth of cannulation in the Outside group was significantly lower than that in the Inside group (p < 0.05). VAS scores were comparable between the Inside and the Outside groups, except at 24 h after surgery. The use of PCA from 24 to 48 h after surgery in the Outside group was significantly higher than that in the Inside group (p < 0.05). The MMSE score and the incidence of POCD in the Outside group were higher than that in the Inside group. At the same time, the serum IL-1β levels at 1 and 6 h after surgery and the serum IL-6 levels at 1, 6, 24, and 48 h after surgery in the Outside group were significantly higher than that in the Inside group (p < 0.05).ConclusionCompared with the outside approach of the FICB, the inside approach of the FICB has better anesthetic effect, better postoperative analgesia, fewer postoperative analgesics, lower incidence of POCD, and lower serum cytokines during the treatment of THA patients.

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Postoperative cognitive dysfunction: an acute approach for the development of novel treatments for neuroinflammation

Cited by 30 publications

References 34 publications

A Noradrenergic Lesion Attenuates Surgery-Induced Cognitive Impairment in Rats by Suppressing Neuroinflammation

A Noradrenergic Lesion Attenuates Surgery-Induced Cognitive Impairment in Rats by Suppressing Neuroinflammation

Electroacupuncture Ameliorates Tibial Fracture-Induced Cognitive Dysfunction by Elevating α7nAChR Expression and Suppressing Mast Cell Degranulation in the Hippocampus of Rats

Anesthetic Effect of the Fascia Iliaca Compartment Block with Different Approaches on Total Hip Arthroplasty and Its Effect on Postoperative Cognitive Dysfunction and Inflammation

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