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Surgery/Anesthesia disturbs mitochondrial fission/fusion dynamics in the brain of aged mice with postoperative delirium.

ABSTRACT: Postoperative delirium (POD) is a common complication following surgery and anesthesia (Surgery/Anesthesia). Mitochondrial dysfunction, which is demonstrated by energy deficits and excessively activated oxidative stress, has been reported to contribute to POD. The dynamic balance between mitochondrial fusion and fission processes is critical in regulating mitochondrial function. However, the impact of Surgery/Anesthesia on mitochondrial fusion/fission dynamics remains unclear. Here, we evaluate the effects of laparotomy under 1.4% isoflurane anesthesia for 2 hours on mitochondrial fission/fusion dynamics in the brain of aged mice. Mice in Surgery/Anesthesia group showed unbalanced fission/fusion dynamics, with decreased DISC1 expression and increased expression of Drp1 and Mfn2 in the mitochondrial fraction, leading to excessive mitochondrial fission and disturbed mitochondrial morphogenesis in the hippocampus and prefrontal cortex. In addition, surgical mice presented mitochondrial dysfunction, demonstrated by abnormally activated oxidative stress (increased ROS level, decreased SOD level) and energy deficits (decreased levels of ATP and MMP). Surgery/Anesthesia also decreased the expression of neuronal/synaptic plasticity-related proteins such as PSD-95 and BDNF. Furthermore, Surgery/Anesthesia induced delirium-like behavior in aged mice. In conclusion, Surgery/Anesthesia disturbed mitochondrial fission/fusion dynamics and then impaired mitochondrial function in the brain of aged mice; these effects may be involved in the underlying mechanism of POD.

SUBMITTER: Lu Y

PROVIDER: S-EPMC6977661 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Surgery/Anesthesia disturbs mitochondrial fission/fusion dynamics in the brain of aged mice with postoperative delirium.

Lu Yayuan Y Chen Lei L Ye Jishi J Chen Chang C Zhou Ying Y Li Ke K Zhang Zongze Z Peng Mian M

Aging 20200112 1

Postoperative delirium (POD) is a common complication following surgery and anesthesia (Surgery/Anesthesia). Mitochondrial dysfunction, which is demonstrated by energy deficits and excessively activated oxidative stress, has been reported to contribute to POD. The dynamic balance between mitochondrial fusion and fission processes is critical in regulating mitochondrial function. However, the impact of Surgery/Anesthesia on mitochondrial fusion/fission dynamics remains unclear. Here, we evaluate ...[more]

PMID: 31929114

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Project description:Delirium after surgery or Postoperative delirium (POD) is an underdiagnosed entity, despite its severity and high incidence. Patients with delirium require a longer hospital stay and present more postoperative complications, which also increases hospital costs. Given its importance and the lack of specific treatment, multifactorial preventive strategies are evidenced based. Our hypothesis is that using general anaesthesia and avoiding the maximum time in excessively deep anaesthetic planes through BIS neuromonitoring device will reduce the incidence of postoperative delirium in patients over the age of 65 and their hospitalization stay. Patients were randomly assigned to two groups: The visible BIS group and the hidden BIS neuromonitoring group. In the visible BIS group, the depth of anaesthesia was sustained between 40 and 60, while in the other group the depth of anaesthesia was guided by hemodynamic parameters and the Minimum Alveolar Concentration value. Patients were assessed three times a day by research staff fully trained during the 72 h after the surgery to determine the presence of POD, and there was follow-up at 30 days. Patients who developed delirium (n = 69) was significantly lower in the visible BIS group (n = 27; 39.1%) than in the hidden BIS group (n = 42, 60.9%; p = 0.043). There were no differences between the subtypes of delirium in the two groups. Patients in the hidden BIS group were kept for 26.6 ± 14.0 min in BIS values < 40 versus 11.6 ± 10.9 min (p < 0.001) for the patients in the visible BIS group. The hospital stay was lower in the visible BIS group 6.56 ± 6.14 days versus the 9.30 ± 7.11 days (p < 0.001) for the hidden BIS group, as well as mortality; hidden BIS 5.80% versus visible BIS 0% (p = 0.01). A BIS-guided depth of anaesthesia is associated with a lower incidence of delirium. Patients with intraoperative neuromonitoring stayed for a shorter time in excessively deep anaesthetic planes and presented a reduction in hospital stay and mortality.

Project description:Mitochondrial dysfunction is a predominant risk factor in ischemic heart disease, in which the imbalance of mitochondrial fusion and fission deteriorates mitochondrial function and might lead to cardiomyocyte death. C-phycocyanin (C-pc), an active component from blue-green algae, such as Spirulina platensis, has been reported to have anti-apoptosis and anti-oxidation functions. In this study, the effects of C-pc on mitochondrial dynamics of cardiomyocytes was examined using an oxygen-glucose deprivation/reoxygenation (OGD/R) model in H9c2 cells, an in vitro model to study the ischemia in the heart. Cell viability assay showed that C-pc dose-dependently reduced OGD/R-induced cell death. Intracellular reactive oxygen species production induced by OGD/R was decreased in C-pc-treated groups in a dose-dependent manner as well. H9c2 cells subjected to OGD/R showed excessive mitochondrial fission and diminished mitochondrial fusion. C-pc treatment significantly ameliorated unbalanced mitochondrial dynamics induced by OGD/R and regulated mitochondrial remodeling through inhibiting mitochondrial fission while promoting fusion. The enhanced expressions of dynamin 1-like protein and mitochondrial fission 1 protein induced by OGD/R were suppressed by C-pc, while the subdued expressions of mitochondrial fusion proteins mitofusins 1 and 2 and optic atrophy 1 induced by OGD/R increased in C-pc-treated groups. Triple immunofluorescence staining revealed that C-pc treatment reduced the recruitment of dynamin 1-like protein from cytoplasm to mitochondrial membranes. Furthermore, C-pc protected H9c2 cells against OGD/R-induced cytochrome c/apoptotic protease activating factor-1 intrinsic apoptosis and suppressed the phosphorylations of extracellular signal-regulated kinase and c-Jun N-terminal kinase. These results suggest that C-pc protects cardiomyocytes from ischemic damage by affecting mitochondrial fission and fusion dynamics and reducing apoptosis and, thus, may be of potential as a prophylactic or therapeutic agent for ischemic heart disease.

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Surgery/Anesthesia disturbs mitochondrial fission/fusion dynamics in the brain of aged mice with postoperative delirium.

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Surgery/Anesthesia disturbs mitochondrial fission/fusion dynamics in the brain of aged mice with postoperative delirium.

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