Critical illness is associated with muscle wasting and muscle weakness. Using burn injury as a model of local and systemic inflammatory response, we tested the hypothesis that thermal injury causes apoptosis in muscle. After a 40% body surface area burn to rats, abdominal muscles beneath the burn and limb muscles distant from the burn were examined for apoptosis at varying times after burn. Ladder assay, ELISA, and histological methods showed evidence of apoptosis in the abdominal muscles within 4–12 h with peak changes occurring at 3–7 days. Maximal apoptosis was also evident at distant limb muscles at 3–7 days. Investigation of proapoptotic pathways indicated mitochondrial membrane potential to be altered by 1 h after burn. Starting at 15 min after burn, cytochrome c was released from the mitochondria into the cytosol, followed by increased activity of caspase-3, starting at 6 h after burn. These studies suggest that mitochondria and caspase-mediated apoptotic pathways may be an additional mechanism of muscle weight loss in burns and may be potential therapeutic targets for prevention of muscle wasting.

Background: Anesthesia during the synaptogenic period induces dendritic spine formation, which may affect neurodevelopment. The authors, therefore, evaluated whether changes in synaptic transmission after dendritic spine formation induced by sevoflurane were associated with long-term behavioral changes. The effects of sevoflurane on mitochondrial function were also assessed to further understand the mechanism behind spinogenesis. Methods: Postnatal day 16 to 17 mice were exposed to sevoflurane (2.5% for 2 h), and synaptic transmission was measured in the medial prefrontal cortex 6 h or 5 days later. The expression of postsynaptic proteins and mitochondrial function were measured after anesthesia. Long-term behavioral changes were assessed in adult mice. Results: Sevoflurane increased the expression of excitatory postsynaptic proteins in male and female mice (n = 3 to 5 per group). Sevoflurane exposure in male mice transiently increased miniature excitatory postsynaptic current frequency (control: 8.53 ± 2.87; sevoflurane: 11.09 ± 2.58) but decreased miniature inhibitory postsynaptic current frequency (control: 10.18 ± 4.66; sevoflurane: 6.88 ± 2.15). Unexpectedly, sevoflurane increased miniature inhibitory postsynaptic current frequency (control: 1.81 ± 1.11; sevoflurane: 3.56 ± 1.74) in female mice (neurons, n = 10 to 21 per group). Sevoflurane also increased mitochondrial respiration in male mice (n = 5 to 8 per group). However, such changes from anesthesia during the critical period did not induce long-term behavioral consequences. Values are presented as mean ± SD. Conclusions: Sevoflurane exposure during the critical period induces mitochondrial hyperactivity and transient imbalance of excitatory/inhibitory synaptic transmission, without long-lasting behavioral consequences. Further studies are needed to confirm sexual differences and to define the role of mitochondrial activity during anesthesia-induced spine formation.

Chahyun Oh, Chan Noh, Hongsik Eom, Sangmin Lee, Seyeon Park, Sunyeul Lee, Yong Sup Shin, Youngkwon Ko, Woosuk Chung, and Boohwi Hong. Korean J Pain 2020;33:144-52. https://doi.org/10.3344/kjp.2020.33.2.144

Recent studies have reported that cancer surgeries involving regional anesthesia have better outcomes than those under general anesthesia. However, the effects of anesthetic technique have not been investigated in patients with bladder cancer. Therefore, this retrospective study was conducted to investigate which anesthetic technique results in a better bladder cancer prognosis. Sixty-one of 531 patients underwent transurethral resection of a bladder tumor under general anesthesia from 2001 to 2008 in our hospital. Patients who attended five years of follow-up and who had pathological findings of urothelial carcinoma grades I–II were enrolled. Finally, 24 patients (G group) who underwent general anesthesia and 137 (R group) who underwent regional (spinal or epidural) anesthesia were compared. Five-year survival and recurrence-free time were compared using the chi-square and t-tests, respectively. A logistic regression and partial correlation analysis were performed to evaluate other factors affecting survival. Five-year survival was 87.5 % for general anesthesia and 96.3 % for regional (P = 0.099). The regression analysis showed that older age contributed to reduced survival (odds ratio = 0.85, P = 0.001). Regional anesthesia showed higher 5-year survival (coefficient = −0.167, P = 0.044) more than general anesthesia through the partial correlation analysis. Though partial correlation analysis show that five-year survival is higher in patients whose surgery is under regional than general anesthesia, the association was not significant in the chi-square test and logistic regression analysis. Large prospective studies are needed to determine whether the association between regional anesthesia and survival is causative.

Apurinic/apyrimidinic endonuclease 1 (APE1), a ubiquitous multipurpose protein, is also known as redox effector factor-1 (Ref-1). It is involved in DNA repair and redox signaling and, in turn, oxidative stress-induced neurodegeneration. Although previous studies have demonstrated that APE1/Ref-1 functions as a negative regulator of inflammatory response via several mechanisms in neuronal cells, little is known about the roles of APE1/Ref-1 in glial cells. In this study, we found that cytoplasmic APE1/Ref-1 expression was upregulated in reactive astrocytes of the kainic acid- or lipopolysaccharide (LPS)-injected hippocampus. Analysis of the inflammatory response induced by extranuclear APE1/Ref-1 (ΔNLS-Ref-1) in cultured primary astrocytes revealed that it markedly suppressed inducible nitric oxide synthase (iNOS) expression and tumor necrosis factor-α (TNF-α) secretion induced by LPS to a similar extent as did wild type APE1/Ref-1 (WT-Ref-1), supporting the concept an anti-inflammatory role of extranuclear APE1/Ref-1 in astrocytes. Additionally, overexpression of WT- and ΔNLS-Ref-1 suppressed the transcriptional activity of nuclear factor-κB (NF-κB), although it effectively enhanced activator protein 1 (AP-1) activity. The blunting effect of APE1/Ref-1 on LPS-induced NF-κB activation was not mediated by IκB kinase (IKK) activity. Instead, APE1/Ref-1 inhibited p300-mediated acetylation of p65 by suppressing intracellular reactive oxygen species (ROS) levels following LPS treatment. Taken together, our results showed that altered expression and/or subcellular distribution of APE1/Ref-1 in activated astrocytes regulated the neuroinflammatory response to excitotoxin and endotoxin insults used in model of neurodegenerative brain diseases.

Chung W, et al. Korean J Anesthesiol. 2017 Dec;70(6):642-647. https://doi.org/10.4097/kjae.2017.70.6.642