The Common Inhalation Anesthetic Isoflurane Induces Apoptosis and Increases Amyloid β Protein Levels

Xie, Zhongcong; Dong, Yuanlin; Maeda, Uta; Alfille, Paul H.; Culley, Deborah J.; Crosby, Gregory; Tanzi, Rudolph E.

doi:10.1097/00000542-200605000-00015

Cited by 268 publications

(263 citation statements)

References 27 publications

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“…The latter has become more pertinent in the advent of an aging population and increasing awareness of the interplay between the perioperative inflammatory state, anesthetic agents, and neurodegenerative processes. [47][48][49][50][51] Assessment of cognitive recovery has thus progressed from simple assessments of orientation and comprehension 38,41,46 to more formal neuropsychological-based assessment. 26,37,52,53 More recent clinical recovery assessment tools, such as the Postoperative Quality of Recovery Scale (PostopQRS), 37 assess cognitive recovery by applying formal neuropsychological tests in truncated form and assessing patient recovery in relation to individual baseline function both in real time and over multiple time points.…”

Section: Measurement Of Recoverymentioning

confidence: 99%

The importance of postoperative quality of recovery: influences, assessment, and clinical and prognostic implications

Bowyer

Royse

2015

Can J Anesth/J Can Anesth

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Quality of recovery is a complex construct whose definition is influenced heavily by the opinions and biases of the individual patient, clinician, or institution. As a result, recovery assessment tools differ in their fundamental definitions of recovery, breadth, and assessment time frame. Accurate assessment of recovery is essential as suboptimal recovery has both economic and prognostic implications. Quality of care is often substituted as a surrogate at the institutional level for quality of recovery, but it is ideologically distinct from patients' perceived quality of care, recovery, and satisfaction. Recovery tools also differ in their assessment of recovery as a continuous vs dichotomous variable and in their focus at the group vs individual level. Ideally, recovery measures should assess outcomes in a simple dichotomous fashion and maintain relevancy by assessing in multiple domains at various time points. Assessment of recovery in a dichotomous fashion also has both clinical and research applications. It allows identification of suboptimal recovery at both individual and group levels, respectively, and when performed in real time, it allows the opportunity for timely targeted intervention specific to individual patients as well as for resource rationalization.Résumé La qualité de récupération est un construit complexe dont la définition est fortement influencée par les opinions et les biais du patient, du clinicien, voire de l'établissement. Dès lors, les outils d'évaluation de la récupération diffèrent de par la définition-même de la récupération, leur envergure, et le cadre temporel de l'évaluation. Une évaluation précise de la récupération est essentielle; en effet, une récupération sous-optimale a des implications tant économiques que pronostiques. Au niveau institutionnel, on utilise souvent la qualité des soins comme substitut de la qualité de récupération mais, d'un point de vue idéologique, ce concept se distingue de la qualité des soins, de la récupération et de la satisfaction telles que perçues par les patients. Les outils de récupération diffèrent également dans leur évaluation de la récupération en tant que variable continue ou dichotomique et dans leur emphase sur le groupe ou l'individu. Dans l'idéal, les mesures de la récupération devraient évaluer les pronostics de manière dichotomique simple et maintenir leur pertinence en évaluant plusieurs domaines à différents moments dans le temps. L'évaluation dichotomique de la récupération a également des applications cliniques et en recherche. Elle permet d'identifier une récupération sous-optimale tant au niveau du groupe que de l'individu. D'autre part, lorsque ce type d'évaluation est réalisé en temps réel, elle nous donne la possibilité d'intervenir d'une manière ciblée et opportune spécifique à chaque patient tout en rationnalisant les ressources.Author contributions Andrea Bowyer and Colin Royse contributed substantially to the conception and design of the manuscript and drafted the version to be published.

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Section: Measurement Of Recoverymentioning

confidence: 99%

The importance of postoperative quality of recovery: influences, assessment, and clinical and prognostic implications

Bowyer

Royse

2015

Can J Anesth/J Can Anesth

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“…Perioperative factors, including hypoxia (Kokmen et al, 1996; Jendroska et al, 1997; Nagy et al, 1997; Snowdon et al, 1997; Kalaria, 2000), hypocapnia (Xie et al, 2004), and anesthetics (Eckenhoff et al, 2004;Xie et al, 2006a), have been reported to potentially contribute to AD neuropathogenesis. These perioperative factors may also cause postoperative cognitive dysfunction, a dementia associated with surgery and anesthesia, by trigging AD neuropathogenesis.…”

Section: Introductionmentioning

confidence: 99%

“…Treatment with a commonly used inhalation anesthetic isoflurane (1.2-2.5% for 6 h) has been shown to enhance A␤ aggregation and cytotoxicity in pheochromocytoma cells (Eckenhoff et al, 2004). We recently showed that a clinically relevant concentration (2%) of isoflurane can induce apoptosis, alter APP processing, and increase production of A␤ in H4 human neuroglioma cells (Xie et al, 2006a).…”

Section: Introductionmentioning

confidence: 99%

The Inhalation Anesthetic Isoflurane Induces a Vicious Cycle of Apoptosis and Amyloid β-Protein Accumulation

Xie¹,

Dong²,

Maeda³

et al. 2007

J. Neurosci.

220

233

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The anesthetic isoflurane has been reported to induce apoptosis and increase A␤ generation and aggregation. However, the molecular mechanism underlying these effects remains unknown. We therefore set out to assess whether the effects of isoflurane on apoptosis are linked to amyloid ␤-protein (A␤) generation and aggregation. For this purpose, we assessed the effects of isoflurane on ␤-site amyloid ␤ precursor protein (APP)-cleaving enzyme (BACE) and ␥-secretase, the proteases responsible for A␤ generation. We also tested the effects of inhibitors of A␤ aggregation (iA␤5, a ␤-sheet breaker peptide; clioquinol, a copper-zinc chelator) on the ability of isoflurane to induce apoptosis. All of these studies were performed on naive human H4 neuroglioma cells as well as those overexpressing APP (H4-APP cells). Isoflurane increased the levels of BACE and ␥-secretase and secreted A␤ in the H4-APP cells. Isoflurane-induced A␤ generation could be blocked by the broad-based caspase inhibitor Z-VAD. The A␤ aggregation inhibitors, iA␤5 and clioquinol, selectively attenuated caspase-3 activation induced by isoflurane. However, isoflurane was able to induce caspase-3 activation in the absence of any detectable alterations of A␤ generation in naive H4 cells. Finally, A␤ potentiated the isoflurane-induced caspase-3 activation in naive H4 cells. Collectively, these findings suggest that isoflurane can induce apoptosis, which, in turn, increases BACE and ␥-secretase levels and A␤ secretion. Isoflurane also promotes A␤ aggregation. Accumulation of aggregated A␤ in the media can then promote apoptosis. The result is a vicious cycle of isoflurane-induced apoptosis, A␤ generation and aggregation, and additional rounds of apoptosis, leading to cell death.

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“…Of course it should be noted that symptomatic pre-operative neurological diseases, including dementia and any disorders of the central nervous system, are considered as exclusion criteria for studies concerning POCD (Monk et al, 2008). Data from experimental models pose the suggestion that exposure to inhaled anaesthetics increases cerebral pathological findings that are normally observed in Alzheimer's disease, including the increase of β-amyloid (Xie et al, 2006). Furthermore, hypothermia during anaesthesia induces hyperphosphorylation of proteins by reducing the phosphatase 2a activity (Planel et al, 2008).…”

Section: Neurological Diseasesmentioning

confidence: 99%

“…Furthermore, hypothermia during anaesthesia induces hyperphosphorylation of proteins by reducing the phosphatase 2a activity (Planel et al, 2008). Finally, it is noteworthy that anaesthesia, only at higher concentrations and prolonged periods, has been reported to produce pathological lesions similar to those of Alzheimer's disease but this is also a fact which is being disputed (Xie et al, 2006;Xie et al, 2007;Donk et al, 2012).…”

Section: Neurological Diseasesmentioning

confidence: 99%

Risk Factors for the Development of Post-Operative Cognitive Dysfunction

Pappa¹,

Theodosiadis²,

Tsounis³

et al. 2016

GJHS

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Background: Many studies have shown that a large number of patients undergoing surgery show a measurable cognitive deterioration after surgery, while many of them still show cognitive deficits even three months later an operation. These specific cognitive deficits in which there is a temporal association between surgery and mental disorders are defined as postoperative impairment of cognitive function. Among cognitive disorders occurring during the postoperative period, the post-operative cognitive dysfunction (POCD) is less studied.Aim: Risk factors concerning POCD will be overviewed in order to be considered as a measure of prevention of POCD.Method: A literature search using combined keywords was undertaken on bibliographic databases including PubMed, Google Scholar and Scopus and through systematic selection 72 scientific articles were identified. Concerning the selection criteria, the material of this study consists of sources published mainly over the last fifteen years, while some articles that published before 2000 were selected because they were considered to be important.Results: These disorders frequently occur in patients of advanced age. It is obvious that as the population of humanity ages, many older people are likely to develop health problems that require surgery and therefore a large number of people are likely to develop post-operative cognitive disorders. For the appearance of POCD, as for other mental disorders (e.g. delirium), several factors are implicated. According to the findings, except the advanced age, genetic polymorphism, idiosyncratic condition, the presence of metabolic syndrome and neurological diseases, the type of anaesthesia and surgical operation and sleep disturbance are among the most important risk factors.

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The Common Inhalation Anesthetic Isoflurane Induces Apoptosis and Increases Amyloid β Protein Levels

Cited by 268 publications

References 27 publications

The importance of postoperative quality of recovery: influences, assessment, and clinical and prognostic implications

The importance of postoperative quality of recovery: influences, assessment, and clinical and prognostic implications

The Inhalation Anesthetic Isoflurane Induces a Vicious Cycle of Apoptosis and Amyloid β-Protein Accumulation

Risk Factors for the Development of Post-Operative Cognitive Dysfunction

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