Involvement of acute neuroinflammation in postoperative delirium-like cognitive deficits in rats

Kawano, Takashi; Yamanaka, Daiki; Aoyama, Bun; Tateiwa, Hiroki; Shigematsu-Locatelli, Marie; Nishigaki, Atsushi; Iwata, Hisato; Locatelli, Fabricio M.; Yokoyama, Masataka

doi:10.1007/s00540-018-2504-x

Cited by 32 publications

(22 citation statements)

References 35 publications

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“…However, TNF‐α was also increased after anesthesia without surgery, but no activation of microglia was found in the hippocampus. It suggests that isoflurane anesthesia alone could not induce harmful inflammation in the hippocampus, which is in line with Wang et al and Kawano et al’s findings 32,33 . Callaway et al 34 and Crosby et al 35 demonstrated that exposure to sevoflurane or isoflurane alone had no impact on learning and memory in the rodent.…”

Section: Discussionsupporting

confidence: 72%

Disruption of the GABAergic system contributes to the development of perioperative neurocognitive disorders after anesthesia and surgery in aged mice

et al. 2020

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Aims Perioperative neurocognitive disorders (PND) are associated with cognitive impairment in the preoperative or postoperative period, and neuroinflammation is thought to be the most important mechanisms especially during the postoperative period. The GABAergic system is easily disrupted by neuroinflammation. This study investigated the impact of the GABAergic system on PND after anesthesia and surgery. Methods An animal model of laparotomy with inhalation anesthesia in 16‐month‐old mice was addressed. Effects of the GABAergic system were assessed using biochemical analysis. Pharmacological blocking of α5GABAARs or P38 mitogen‐activated protein kinase (MAPK) were applied to investigate the effects of the GABAergic system. Results After laparotomy, the hippocampus‐dependent memory and long‐term potentiation were impaired, the levels of IL‐6, IL‐1β and TNF‐α up‐regulated in the hippocampus, the concentration of GABA decreased, and the protein levels of the surface α5GABAARs up‐regulated. Pharmacological blocking of α5GABAARs with L655,708 alleviated laparotomy induced cognitive deficits. Further studies found that the P38 MAPK signaling pathway was involved and pharmacological blocking with SB203,580 alleviated memory dysfunctions. Conclusions Anesthesia and surgery caused neuroinflammation in the hippocampus, which consequently disrupted the GABAergic system, increased the expressions of surface α5GABAARs especially through the P38 MAPK signaling pathway, and eventually led to hippocampus‐dependent memory dysfunctions.

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Section: Discussionsupporting

confidence: 72%

Disruption of the GABAergic system contributes to the development of perioperative neurocognitive disorders after anesthesia and surgery in aged mice

et al. 2020

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“…A recent study suggested the involvement of neuroinflammation in postoperative delirium-like cognitive deficits [13]. We tested whether propofol could impact the expression level of IL-6 in the brain tissues of these mice.…”

Section: Resultsmentioning

confidence: 99%

Propofol Induces Postoperative Depression and Inhibits Microglial Function in Mice

Song

Meng

2019

Mediators of Inflammation

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Many patients experience excellent physical recoveries after surgery; however, there are some of them who from suffer mood fluctuation, even depression. Postoperative depression may be resulted from cognitive dysfunction, pain, and a compromised immune system during the surgery. But there is a higher possibility that general anaesthesia may be responsible for the development of depression. Here, we employed one of the most used anaesthetics, propofol, in a mouse model to investigate whether this intravenous anaesthetic compound could cause depressive-like behavioural performance in mice. We found a single dose of propofol caused significant abnormal behavioural performance in tail suspension, forced swimming, and open field tests. We also examined the brain section of these mice and revealed that there was significant reduced expression of the CD11b protein, which demonstrated an inhibition of propofol on microglial function. We investigated the effect of propofol on synaptic protein, SYP, and found there was no notable influence on the protein expression. These above results suggested that propofol treatment might promote the depressive-like behaviours in mice via influencing the microglial cell function. Furthermore, we found the level of the IL-6 cytokine was significantly increased in the brain tissue, which might subsequently cause the activation of the transcriptional factor, STAT3. Our finding may provide a new perspective of further understanding the mechanism of anaesthetic drugs and deciphering the underlying mechanism of postoperative depression.

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“…In animal studies, research has shown that surgery increases the risk of cognitive impairment when compared with exposure to anesthesia alone [69, 70]. One study established a model of abdominal surgery under local anesthesia alone to assess the effects of surgery without the confounding risk of sedative or anesthesia exposure.…”

Section: Main Bodymentioning

confidence: 99%

“…In animal studies, there is mixed evidence regarding whether volatile agents increase pro-inflammatory cytokines and/or microglial activation in the absence of surgery. Although an increase in inflammation has been observed by some groups [75, 103–105], other groups have reported no effect of isoflurane or sevoflurane anesthesia alone on microglial activation and/or proinflammatory cytokine expression [70, 82, 106, 107]. The mechanism for induction of neuroinflammation following exposure to anesthesia with or without surgery continues to be actively investigated.…”

Section: Main Bodymentioning

confidence: 99%

Anesthesiology and cognitive impairment: a narrative review of current clinical literature

2019

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Background: The impact of general anesthesia on cognitive impairment is controversial and complex. A large body of evidence supports the association between exposure to surgery under general anesthesia and development of delayed neurocognitive recovery in a subset of patients. Existing literature continues to debate whether these short-term effects on cognition can be attributed to anesthetic agents themselves, or whether other variables are causative of the observed changes in cognition. Furthermore, there is conflicting data on the relationship between anesthesia exposure and the development of long-term neurocognitive disorders, or development of incident dementia in the patient population with normal preoperative cognitive function. Patients with pre-existing cognitive impairment present a unique set of anesthetic considerations, including potential medication interactions, challenges with cooperation during assessment and non-general anesthesia techniques, and the possibility that pre-existing cognitive impairment may impart a susceptibility to further cognitive dysfunction. Main body: This review highlights landmark and recent studies in the field, and explores potential mechanisms involved in perioperative cognitive disorders (also known as postoperative cognitive dysfunction, POCD). Specifically, we will review clinical and preclinical evidence which implicates alterations to tau protein, inflammation, calcium dysregulation, and mitochondrial dysfunction. As our population ages and the prevalence of Alzheimer's disease and other forms of dementia continues to increase, we require a greater understanding of potential modifiable factors that impact perioperative cognitive impairment. Conclusions: Future research should aim to further characterize the associated risk factors and determine whether certain anesthetic approaches or other interventions may lower the potential risk which may be conferred by anesthesia and/or surgery in susceptible individuals.

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Involvement of acute neuroinflammation in postoperative delirium-like cognitive deficits in rats

Cited by 32 publications

References 35 publications

Disruption of the GABAergic system contributes to the development of perioperative neurocognitive disorders after anesthesia and surgery in aged mice

Disruption of the GABAergic system contributes to the development of perioperative neurocognitive disorders after anesthesia and surgery in aged mice

Propofol Induces Postoperative Depression and Inhibits Microglial Function in Mice

Anesthesiology and cognitive impairment: a narrative review of current clinical literature

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