The Effects of Isoflurane and Desflurane on Cognitive Function in Humans

Zhang, Bin; Tian, Ming; Yu, Zhengtao; Yen, Yun; Sherman, Janet C.; Li, Shuren; Tanzi, Rudolph E.; Marcantonio, Edward R.; Xie, Zhongcong

doi:10.1097/sa.0b013e318269d3d4

Cited by 5 publications

(6 citation statements)

References 37 publications

(55 reference statements)

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“…Isoflurane, one of the most widely used inhalational anaesthetics, is extensively used beyond surgical interventions, including painless induced delivery or endoscopy. Previously, results from our lab and other studies demonstrated that cognitive functions were significantly impaired following isoflurane anaesthesia in both human and mice (Zhang B et al 2012;Xia et al 2016;Fang et al 2017;Ni et al 2017;Zuo et al 2018). It has also been reported that isoflurane causes severe oxidative stress by impairing antioxidant enzymes, inducing mitochondrial dysfunction and increasing the levels of ROS .…”

Section: Discussionmentioning

confidence: 62%

Protective effects of grape seed procyanidin on isoflurane-induced cognitive impairment in mice

Gong

Fang

et al. 2020

Pharmaceutical Biology

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Context: Oxidative imbalance-induced cognitive impairment is among the most urgent clinical concerns. Isoflurane has been demonstrated to impair cognitive function via an increase in oxidative stress. GSP has strong antioxidant capacities, suggesting potential cognitive benefits. Objective: This study investigates whether GSP pre-treatment can alleviate isoflurane-induced cognitive dysfunction in mice. Materials and methods: C57BL/6J mice were pre-treated with either GSP 25-100 mg/kg/d for seven days or GSP 100-400 mg/kg as a single dose before the 6 h isoflurane anaesthesia. Cognitive functioning was examined using the fear conditioning tests. The levels of SOD, p-NR2B and p-CREB in the hippocampus were also analysed. Results: Pre-treatment with either a dose of GSP 50 mg/kg/d for seven days or a single dose of GSP 200 mg/kg significantly increased the % freezing time in contextual tests on the 1st (72.18 ± 12.39% vs. 37.60 ± 8.93%; 78.27 ± 8.46% vs. 52.72 ± 2.64%), 3rd (93.80 ± 7.62% vs. 52.94 ± 14.10%; 87.65 ± 10.86% vs. 52.89 ± 1.73%) and 7th (91.36 ± 5.31% vs. 64.09 ± 14.46%; 93.78 ± 3.92% vs. 79.17 ± 1.79%) day after anaesthesia. In the hippocampus of mice exposed to isoflurane, GSP 200 mg/kg increased the total SOD activity on the 1st and 3rd day and reversed the decreased activity of the NR2B/CREB pathway. Discussion and conclusions: These findings suggest that GSP improves isoflurane-induced cognitive dysfunction by protecting against perturbing antioxidant enzyme activities and NR2B/CREB pathway. Therefore, GSP may possess a potential prophylactic role in isoflurane-induced and other oxidative stressrelated cognitive decline.

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Section: Discussionmentioning

confidence: 62%

Protective effects of grape seed procyanidin on isoflurane-induced cognitive impairment in mice

Gong

Fang

et al. 2020

Pharmaceutical Biology

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“…The mPTP opening blocker CsA can mitigate the isoflurane‐induced impairment of learning and memory. These results, together with findings that desflurane anesthesia may lead to a lesser degree of cognitive decline in humans than isoflurance anesthesia,36 suggest that desflurane could be a better choice of anesthetic than isoflurane for AD patients who are susceptible to development of cognitive function decline, pending further human studies. Furthermore, these findings suggest that mitochondrial function (eg, opening of mPTP) could be among the molecular mechanisms responsible for different effects of isoflurane and desflurane on function of learning and memory.…”

Section: Discussionmentioning

confidence: 96%

Anesthetics isoflurane and desflurane differently affect mitochondrial function, learning, and memory

Zhang

Wang

et al. 2012

Annals of Neurology

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205

226

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Objective There are approximately 8.5 million Alzheimer disease (AD) patients who need anesthesia and surgery care every year. The inhalation anesthetic isoflurane, but not desflurane, has been shown to induce caspase activation and apoptosis, which are part of AD neuropathogenesis, through the mitochondria-dependent apoptosis pathway. However, the in vivo relevance, underlying mechanisms, and functional consequences of these findings remain largely to be determined. Methods We therefore set out to assess the effects of isoflurane and desflurane on mitochondrial function, cytotoxicity, learning, and memory using flow cytometry, confocal microscopy, Western blot analysis, immunocytochemistry, and the fear conditioning test. Results Here we show that isoflurane, but not desflurane, induces opening of mitochondrial permeability transition pore (mPTP), increase in levels of reactive oxygen species, reduction in levels of mitochondrial membrane potential and adenosine-5′-triphosphate, activation of caspase 3, and impairment of learning and memory in cultured cells, mouse hippocampus neurons, mouse hippocampus, and mice. Moreover, cyclosporine A, a blocker of mPTP opening, attenuates isoflurane-induced mPTP opening, caspase 3 activation, and impairment of learning and memory. Finally, isoflurane may induce the opening of mPTP via increasing levels of reactive oxygen species. Interpretation These findings suggest that desflurane could be a safer anesthetic for AD patients as compared to isoflurane, and elucidate the potential mitochondria-associated underlying mechanisms, and therefore have implications for use of anesthetics in AD patients, pending human study confirmation.

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“…For example, some studies suggest that deep anaesthesia (as determined using bispectral index monitoring) is associated with higher incidence of POCD 58 whereas others suggest no association between the depth of anaesthesia and POCD. 59 A pilot study by Zhang and colleagues 60 suggested that perhaps isoflurane might be more likely to cause POCD when compared with desflurane although large-scale studies would be necessary to confirm this notion.…”

Section: Anaesthesia-induced Neurotoxicity and Neuroplasticity In Thementioning

confidence: 99%

“…19 82 Although the clinical relevance of these differences between isoflurane and desflurane remains to be determined, a pilot human study suggests that surgery under anaesthesia with isoflurane, but not desflurane, can lead to cognitive dysfunction in patients. 60 Protection for cognitive dysfunction by overexpression of heat-shock protein 72…”

Section: Agent-specific Differences In Neurotoxicitymentioning

confidence: 99%

Anaesthetic neurotoxicity and neuroplasticity: an expert group report and statement based on the BJA Salzburg Seminar

Jevtović-Todorović

Absalom

Blomgren

et al. 2013

British Journal of Anaesthesia

245

182

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Although previously considered entirely reversible, general anaesthesia is now being viewed as a potentially significant risk to cognitive performance at both extremes of age. A large body of preclinical as well as some retrospective clinical evidence suggest that exposure to general anaesthesia could be detrimental to cognitive development in young subjects, and might also contribute to accelerated cognitive decline in the elderly. A group of experts in anaesthetic neuropharmacology and neurotoxicity convened in Salzburg, Austria for the BJA Salzburg Seminar on Anaesthetic Neurotoxicity and Neuroplasticity. This focused workshop was sponsored by the British Journal of Anaesthesia to review and critically assess currently available evidence from animal and human studies, and to consider the direction of future research. It was concluded that mounting evidence from preclinical studies reveals general anaesthetics to be powerful modulators of neuronal development and function, which could contribute to detrimental behavioural outcomes. However, definitive clinical data remain elusive. Since general anaesthesia often cannot be avoided regardless of patient age, it is important to understand the complex mechanisms and effects involved in anaesthesia-induced neurotoxicity, and to develop strategies for avoiding or limiting potential brain injury through evidence-based approaches.

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The Effects of Isoflurane and Desflurane on Cognitive Function in Humans

Cited by 5 publications

References 37 publications

Protective effects of grape seed procyanidin on isoflurane-induced cognitive impairment in mice

Protective effects of grape seed procyanidin on isoflurane-induced cognitive impairment in mice

Anesthetics isoflurane and desflurane differently affect mitochondrial function, learning, and memory

Anaesthetic neurotoxicity and neuroplasticity: an expert group report and statement based on the BJA Salzburg Seminar

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