Postoperative Impairment of Cognitive Function in Rats

Wan, Yizhou; Xu, Jing; Ma, Daqing; Yin-ming, Zeng; Cibelli, Mario; Maze, Mervyn

doi:10.1097/00000542-200703000-00007

Cited by 353 publications

(135 citation statements)

References 35 publications

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“…subjected anesthetized rats to splenectomy vs no surgery and demonstrated that there was a period of cognitive dysfunction in the splenectomized rats, as assessed by performance in a Y-maze, which was associated with biochemical markers of hippocampal glial cell activation and inflammation. 8 In another recent study, Wan et al . showed that partial hepatectomy under general anesthesia in 16-month-old mice induced learning and memory impairment as demonstrated by Morris Water Maze performance as well as gliosis, Aβ accumulation, and tau protein phosphorylation as compared with anesthetized controls.…”

Section: Evidence For Anesthesia-mediated Neurodegenerationmentioning

confidence: 93%

“…Thus, reduced reserve and increased vulnerability lead to functional impairment from neural insults, such as oxidative stress or toxin exposure. Current hypotheses attribute the neurotoxic effects of volatile anesthetics to direct toxic effects (e.g., via altered calcium homeostasis), 6 enhancement of endogenous neurodegenerative mechanisms (e.g., increased production of Aβ), 7 neuroinflammation triggered by surgically-induced systemic inflammation, 8 or age-sensitive suppression of stem cell proliferation or differentiation. 9 …”

Section: Anesthetic Neurotoxicitymentioning

confidence: 99%

“…44 Interestingly, the anesthetized rats and mice in these studies that did not undergo surgery showed none of the changes in maze performance or inflammatory markers, suggesting that observed changes were not related to anesthesia alone. In addition, the anesthesia used in these studies was fentanyl plus droperidol 8 and chloral hydrate. 44 Therefore, it remains to be determined whether the volatile anesthetics (e.g., isoflurane) that have been shown to induce apoptosis, Aβ accumulation, and tau phosphorylation can lead to learning and memory impairment in the same rodent model of surgery vs no surgery.…”

Section: Evidence For Anesthesia-mediated Neurodegenerationmentioning

confidence: 99%

See 2 more Smart Citations

Brief review: Anesthetic neurotoxicity in the elderly, cognitive dysfunction and Alzheimer’s disease

Bittner

Yue

Xie

2010

Can J Anesth/J Can Anesth

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Purpose Postoperative cognitive decline in the elderly has emerged as a major health concern. In addition, there is a growing interest in the potential relationship between general anesthetic exposure and the onset and progression of Alzheimer’s disease (AD). The available evidence of a possible association between anesthesia, surgery, and long-term cognitive effects, including AD, deserves consideration. In this review, we summarize the evidence for anesthesia-induced neurotoxicity in the elderly, while highlighting the limitations of existing data, and we put the literature into perspective for the clinician. Principal findings A growing body of evidence suggests that general anesthetics may be neurotoxic to both young and aging brains. Much of the evidence originates from in vitro and in vivo studies with cells, rodents, and nonhuman primates. Despite the animal data suggesting a relationship between anesthesia and neurotoxicity in the elderly, a definitive link remains elusive in humans. Conclusions The possible relation between anesthetic neurotoxicity, postoperative cognitive dysfunction, and AD remains elusive. It remains unclear whether postoperative cognitive decline in the elderly is related more to perioperative stress and related medical co-morbidities.

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Section: Evidence For Anesthesia-mediated Neurodegenerationmentioning

confidence: 93%

Section: Anesthetic Neurotoxicitymentioning

confidence: 99%

Section: Evidence For Anesthesia-mediated Neurodegenerationmentioning

confidence: 99%

See 1 more Smart Citation

Brief review: Anesthetic neurotoxicity in the elderly, cognitive dysfunction and Alzheimer’s disease

Bittner

Yue

Xie

2010

Can J Anesth/J Can Anesth

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show abstract

“…Neuroinflammation, including increases in levels of pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), as well as microglia activation, has been reported to contribute to the cognitive impairment induced by surgery under anesthesia ([6], [7], [8], [9], reviewed in [10]). However, whether the peripheral surgical wounding without the influence of general anesthesia can induce an age dependent neuroinflammation has not been investigated.…”

Section: Introductionmentioning

confidence: 99%

“…We chose TNF-α and IL-6 in the current studies because these two pre-inflammatory cytokines have been shown to be associated with the neuroinflammation associated with surgery under anesthesia ([6], [7], [8], [9], [11], reviewed in [10]). Finally, CD33 is a newly suggested AD associated gene [12].…”

Section: Introductionmentioning

confidence: 99%

Peripheral Surgical Wounding and Age-Dependent Neuroinflammation in Mice

Dong

Wang

et al. 2014

PLoS ONE

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Post-operative cognitive dysfunction is associated with morbidity and mortality. However, its neuropathogenesis remains largely to be determined. Neuroinflammation and accumulation of β-amyloid (Aβ) have been reported to contribute to cognitive dysfunction in humans and cognitive impairment in animals. Our recent studies have established a pre-clinical model in mice, and have found that the peripheral surgical wounding without the influence of general anesthesia induces an age-dependent Aβ accumulation and cognitive impairment in mice. We therefore set out to assess the effects of peripheral surgical wounding, in the absence of general anesthesia, on neuroinflammation in mice with different ages. Abdominal surgery under local anesthesia was established in 9 and 18 month-old mice. The levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), Iba1 positive cells (the marker of microglia activation), CD33, and cognitive function in mice were determined. The peripheral surgical wounding increased the levels of TNF-α, IL-6, and Iba1 positive cells in the hippocampus of both 9 and 18 month-old mice, and age potentiated these effects. The peripheral surgical wounding increased the levels of CD33 in the hippocampus of 18, but not 9, month-old mice. Finally, anti-inflammatory drug ibuprofen ameliorated the peripheral surgical wounding-induced cognitive impairment in 18 month-old mice. These data suggested that the peripheral surgical wounding could induce an age-dependent neuroinflammation and elevation of CD33 levels in the hippocampus of mice, which could lead to cognitive impairment in aged mice. Pending further studies, anti-inflammatory therapies may reduce the risk of postoperative cognitive dysfunction in elderly patients.

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Role of interleukin‐1β in postoperative cognitive dysfunction

Cibelli¹,

Fidalgo²,

Terrando³

et al. 2010

Annals of Neurology

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659

624

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Objective Although postoperative cognitive dysfunction (POCD) often complicates recovery from major surgery, the pathogenic mechanisms remain unknown. We explored whether systemic inflammation, in response to surgical trauma, triggers hippocampal inflammation and subsequent memory impairment, in a mouse model of orthopedic surgery. Methods C57BL/6J, knock out (lacking interleukin [IL]-1 receptor, IL-1R−/−) and wild type mice underwent surgery of the tibia under general anesthesia. Separate cohorts of animals were tested for memory function with fear conditioning tests, or euthanized at different times to assess levels of systemic and hippocampal cytokines and microglial activation; the effects of interventions, designed to interrupt inflammation (specifically and nonspecifically), were also assessed. Results Surgery caused hippocampal-dependent memory impairment that was associated with increased plasma cytokines, as well as reactive microgliosis and IL-1β transcription and expression in the hippocampus. Nonspecific attenuation of innate immunity with minocycline prevented surgery-induced changes. Functional inhibition of IL-1β, both in mice pretreated with IL-1 receptor antagonist and in IL-1R−/− mice, mitigated the neuroinflammatory effects of surgery and memory dysfunction. Interpretation A peripheral surgery-induced innate immune response triggers an IL-1β-mediated inflammatory process in the hippocampus that underlies memory impairment. This may represent a viable target to interrupt the pathogenesis of postoperative cognitive dysfunction.

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Postoperative Impairment of Cognitive Function in Rats

Abstract: These results suggest that splenectomy performed during neuroleptic anesthesia triggers a cognitive decline that is associated with a hippocampal inflammatory response that seems to be due to proinflammatory cytokine-dependent activation of glial cells.

Cited by 353 publications

References 35 publications

Brief review: Anesthetic neurotoxicity in the elderly, cognitive dysfunction and Alzheimer’s disease

Brief review: Anesthetic neurotoxicity in the elderly, cognitive dysfunction and Alzheimer’s disease

Peripheral Surgical Wounding and Age-Dependent Neuroinflammation in Mice

Role of interleukin‐1β in postoperative cognitive dysfunction

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