scholarly journals Effects of L-655,708 on expression changes of GABA, glutamate, and beta-endorphin induced by propofol anesthesia in rats

2018 ◽  
Vol 16 ◽  
pp. 205873921879670
Author(s):  
Jin Wang ◽  
Xinyi Li ◽  
Huisheng Wu ◽  
Jianjuan Ke ◽  
Zongze Zhang ◽  
...  

Anesthetics are considered to be one of the important inducing factors of postoperative cognitive dysfunction (POCD). The hippocampal region of the rat is one of the action sites of general anesthesia drugs. L 655,708, a reverse agonist of gamma aminobutyric acid (GABA) receptor, can significantly improve short-term memory dysfunction in mice after anesthetized with isoflurane. So the purpose of this study is to investigate the effects of L-655,708 on expression of GABA, glutamate (GLU), and beta-endorphin (β-EP) in the dentate gyrus region of the hippocampus and cognition of rats anesthetized with propofol. In all, 30 male Sprague–Dawley (SD) rats were randomly allocated into the control group, sham group, and L-655,708 group, with 10 in each group. The cognitive function of rats was measured by Morris water maze before and 1 h after administration. Then the rats were sacrificed for brain tissues. Immunohistochemistry was used to study the expression of GABA, GLU, and β-EP in the hippocampus of anesthetized rats in each group. Compared with the control group, the latency of the sham group and L-655,708 group were significantly prolonged after administration ( P < 0.05). However, L-655,708 could shorten the prolonged latency ( P < 0.05). There was no significant difference in times of accessing original platform area between the three groups before and after medication ( P > 0.05). The expression level of GABA in the dentate gyrus region of hippocampus of rats in the sham group was significantly higher than that in the control group ( P < 0.05), while the expression level in the L-655,708 group was significantly lower than that in the sham group ( P < 0.05). No significant difference was found in the expression of GLU in the dentate gyrus region of hippocampus of rats in each group ( P > 0.05). Compared with the control group, the expression of β-EP was significantly lower in the dentate gyrus region of the hippocampus of sham group rats ( P < 0.05). However, the expression of β-EP in the L-655,708 group was significantly higher than that in the sham group ( P < 0.05). Cognitive dysfunction in rats anesthetized with propofol may be related to high expression of GABA and low expression of β-EP in the hippocampus. The mechanism of L-655,708 in reducing the cognitive impairment in propofol anesthetized rats may be bound up with down-regulating the expression of GABA and increasing the expression of β-EP in the hippocampus.

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Yue Li ◽  
Dan Huang ◽  
Diansan Su ◽  
Jie Chen ◽  
Liqun Yang

Abstract Background The incidence and risk factors of postoperative cognitive dysfunction (POCD) during robot-assisted radical cystectomy (RARC) in extreme Trendelenburg positioning and pneumoperitoneum are still controversial. The aim of this prospective observational study was to find the incidence rate as well as possible risk factors of POCD in RARC with cerebral oxygen monitoring. Methods Patients who underwent RARC and open abdominal surgery in horizontal positioning were included. Preoperative and postoperative arterial blood gas (ABG), S-100β, C-reactive protein (CRP), and cognitive dysfunction scales were tested. Also, we used Z score to analyze and comprehensively evaluate POCD. Measurements of heart rate (HR), mean arterial pressure (MAP), central venous pressure (CVP), end-tidal CO2 (etCO2), and cerebral oxygen were immediately obtained after different time points during the surgery. Results Here, 24 and 23 patients were included in the RARC group and in the control group, respectively. The incidence of POCD didn’t have significant difference in RARC group (45.8%), in contrast to the control group (26.1%). The laboratory tests of s100β and CRP between two groups didn’t contain significant difference as well. As duration of Trendelenburg and pneumoperitoneum prolonged, the cerebral oxygen saturation in the RARC group increased, which didn’t cause excessive perfusion nevertheless (rSO2<75%). We compared laboratory tests, age, education status, blood loss, and fluid input between POCD and non-POCD patients. A significant difference was found in the serum concentrations of CRP (72.59 ± 42.09 vs. 48.50 ± 26.53, P = 0.025) and age (69.20 ± 7.033 vs. 65.34 ± 5.228, P = 0.041). Conclusion RARC in extreme Trendelenburg positioning and pneumoperitoneum did not significantly increase the incidence of POCD and didn’t cause excessive perfusion. The inflammation marker CRP and age might be independent risk factors of POCD. Trial registration Clinicaltrials.gov with registration number NCT03372135. Registered 1 November 2017 (retrospectively registered).


Author(s):  
Milad Borji ◽  
Somaye Pouy ◽  
Yasaman Yaghobi ◽  
Bahram Naderi Nabi

AbstractBackground and objectivesTonsillectomy is one of the most commonly used pediatric surgeries with high stress levels for children and their parents. The present study was designed and implemented regarding the fact that limited studies have ever been carried out about the effects of complementary therapies such as acupressure on the preoperative anxiety levels in children throughout the world.Materials and methodsPresent study was a randomized clinical trial that was done in three groups with 144 children aged 5–12 years undergoing tonsillectomy. In present study, the children were allocated in three groups: intervention, control and sham. In the intervention group, the acupressure was applied on the Yintang point and in the sham group, was applied at a sham acupoint. No intervention was performed in the control group. Before and after intervention, the pediatric anxiety levels were measured using instruments. The results were analyzed using descriptive and inferential statistics such as the Kruskal-Wallis and Wilcoxon tests, chi-square (χ2) and analysis of variance (ANOVA) test. The significance level was considered p < 0.05.ResultsThe total anxiety score in children was (70.39 ± 20.93) in the control group, (67.83 ± 16.78) in the intervention group and (71.40 ± 21.82) in the sham group, not significant difference (p > 0.05). The different in the overall anxiety score among children before intervention compare to after intervention was as following: Control group (–3 ± 17.46), intervention group (8.42 ± 32.98) and sham group (–4.32 ± 24.47).ConclusionLike other surgical procedures, the tonsillectomy has serious stress for children. Our study demonstrates that the acupressure has a significant effect on the level of preoperative anxiety in children undergoing surgery. Therefore, nurses can use this technique to reduce the pediatric anxiety.


Author(s):  
Mani Arsalan ◽  
Stefan Dhein ◽  
Heike Aupperle ◽  
Ardawan Julian Rastan ◽  
Markus Jan Barten ◽  
...  

Objective The transplantation of mesenchymal stem cells (MSCs) represents a promising approach for treating the ischemic and the nonischemic diseased heart. The positive effects of transplanting these cells could be shown, but the exact mechanisms remain unknown. We evaluated whether the injection site affects the improvement in left ventricular (LV) ejection fraction (EF) and angiogenesis in doxorubicin (Dox)–induced failing hearts. Methods Heart failure was induced in New Zealand white rabbits by doxorubicin treatment, followed by right ventricular MSC transplantation (RV-MSC, n = 6), LV MSC transplantation (LV-MSC, n = 6), sham treatment (sham group, n = 6), or no therapy (Dox group, n = 5). Healthy rabbits were used as control group (n = 8). Cells were isolated after bone marrow aspiration and transplanted locally into the ventricular myocardium. After 4 weeks, cardiac function and capillary density (CD31 staining) were measured. Results The transplantation of MSCs increased the EF significantly (LV-MSC, 39.0% ± 1.4%, and RV-MSC, 39.2% ± 2.6%, vs sham group, 29.8% ± 3.7%; P < 0.001), without significance between the MSC groups ( P = 0.858). Neither the evidence of a transdifferentiation nor any signs of cell engraftment of transplanted cells could be found. The capillary density (capillaries/high-power field) increased in both MSC groups compared with the sham group (LV-MSC by 8.3% ± 3.4%; and RV-MSC, 8.1% ± 2.2%; P < 0.05), without significance between the two MSC groups ( P = 0.927). Conclusions Injection of autologous MSCs in doxorubicin-induced cardiomyopathic rabbit hearts improves EF and enhances angiogenesis. Despite local application, we observed global effects on heart function and capillary density without significant difference between right and LV injection. The paracrine mechanism might be one possible explanation for these findings.


2020 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Mahmoud Hussein Bahr ◽  
Samaa A Kasem Rashwan ◽  
Doaa Abu Elkassim Rashwan

Objectives: Postoperative cognitive dysfunction (POCD) is multifactorial, which may be caused by anesthetic and surgical causes or cerebral injury. This study aimed to evaluate the effect of dexmedetomidine as a neuroprotective drug compared to esmolol on the prevalence of POCD in adult patients undergoing middle ear surgeries under hypotensive anesthesia. Methods: This study included male and female adult patients, according to American Society of Anesthesiology physical status (ASA) I, the patients who underwent middle ear surgeries under hypotensive anesthesia were randomly assigned to two groups that received esmolol and dexmedetomidine. The demographic data, heart rate, mean arterial blood pressure, duration of the surgery, evaluation of the surgical field, and the Mini-Mental State Examination (MMSE) (preoperatively and at 1, 6 and 24 hours postoperatively) were recorded. Results: There was a significant difference between the numbers of patients who had POCD in MMSE1: 12 cases in the esmolol group (41.37%) compared to three cases in the dexmedetomidine group (10.34%) (P = 0.016), in MMSE6: 10 cases in the esmolol group (34.48%) compared with two cases in the dexmedetomidine group (6.89%) (P = 0.023) and in MMSE24: seven cases in the esmolol group (24.13%) compared with one case in the dexmedetomidine group (3.44%) (P = 0.022), while the median and range of MMSE score were comparable between the two groups (P > 0.05). Conclusions: This study suggests that intraoperative use of dexmedetomidine as an adjuvant to hypotensive anesthesia reduces the incidence of POCD compared to esmolol.


2014 ◽  
Vol 26 (1) ◽  
pp. 212 ◽  
Author(s):  
F. Lu ◽  
Y. Lao ◽  
H. Sun ◽  
C. Lei ◽  
Y. Deng ◽  
...  

In this study, to explore the effects and mechanism of Wnt/β-catenin signalling pathway on the maintenance of pluripotency of buffalo embryonic stem-cell-like cells (buffalo ESC-like cells), the GSK3 inhibitors BIO and CHIR99021 were added throughout the experiment – i.e. from buffalo inner cell mass (ICM) culture to ESC-like line generation. The buffalo ICM were respectively cultured in the medium containing 0.5 μg mL–1 BIO and 5 mmol L–1 CHIR99021. The percentage of ICMs attachment and primary colony formation were observed, and found that there was no significant difference in the ICMs attachment rate among of the BIO, CHIR99021, and the control groups (91.18% and 92.98% v. 94.59%; P > 0.05). Treating ICMs with CHIR99021 resulted in more primary colony formation rate compared with the control group (77.71% v. 55.41%; P < 0.05). The proliferation rate of primary colonies of buffalo ESC-like cells was detected by bromodeoxyuridine immunofluorescence techniques. The results show that the proliferation rate of primary colonies in the group of buffalo ESC-like cells treated with CHIR99021 was significantly higher than that of the control group on Day 1, Day 3, Day 4, and Day 5 (P < 0.05), and it was also evidently higher than that of control group only on Day 1 (P < 0.05) in the group of BIO, but there was no significant difference in other days (P > 0.05). The mRNA expression level of proliferation marker PCNA of ESC-like cells was significantly up-regulated in both CHIR99021 and BIO treatment groups (P < 0.05), however, treating buffalo ESC-like cells with CHIR99021 significantly up-regulated the expression of pluripotent gene Oct4 and Sox2 (P < 0.05), but had no effect on pluripotent gene Nanog expression (P > 0.05). Oct4 expression was significantly increased (P < 0.05), and the expression of Sox2 and Nanog were significantly decreased (P < 0.05) in the group of BIO treatment. Furthermore, the relative protein level of β-catenin (the downstream effector of Wnt/β-catenin signalling pathway) and the mRNA expression level of c-Myc (the downstream target gene of Wnt/β-catenin signalling pathway) were significantly increased when buffalo ESC-like cells respectively treated with CHIR99021 and BIO (P < 0.05). In conclusion, treating buffalo ESC-like cells with GSK3 inhibitors CHIR99021 can promote proliferation of buffalo ESC-like cells, maintain their undifferentiated state, and up-regulate the expression levels of β-Catenin and c-Myc in buffalo ESC-like cells. These results indicate that Wnt/β-catenin signalling pathway plays an important role in regulation of self-renewal of buffalo ESC-like cells. This work was funded by the China High Technology Development Program (2011AA100607), China Natural Science Foundation (31072033), and Guangxi Science Foundation (2012GXNSFFA060004).


2020 ◽  
Vol 17 (1) ◽  
pp. 79-85
Author(s):  
Jun-Bao Fu ◽  
Zhi-Hua Wang ◽  
Yong-Ying Ren

Purpose: The current study was conducted in order to investigate the role of Forkhead box O1 and p21-mediated macrophage polarization in postoperative cognitive dysfunction induced by sevoflurane. Methods: There involved a total of 30 healthy mice that were randomly divided into two groups: control group (without any treatment) and anaesthesia group (treated with sevoflurane inhalation). The effects of sevoflurane on cognitive function (memory) in mice were studied by trace fear conditioned reflex, and the effects of systemic inflammation and behavior after operation were measured by enzyme-linked immunosorbent assay (ELISA), the concentrations of CD163 and tumor necrosis factor-α (TNF-α) were measured. The expression of macrophage phenotype was observed by immunofluorescence staining, the expression levels of M1 and M2 markers mRNA were detected by real-time fluorescence quantitative PCR (RT-PCR), and the expression levels of FoxO1 and p21 were analyzed by immunoblotting (Western blot). Results: Compared with the control group, the freezing time in the anesthesia group was lower than that in the control group (P<0.01), indicating that sevoflurane anesthesia led to the decrease of cognitive ability. The blood concentrations of CD163 and TNF-α increased significantly at 24 h after the operation with sevoflurane anesthesia (P<0.05). Fluorescence microscopic observation showed that M2 was the main type of macrophages in normal tissues, while M1 and M2 phenotypes were highly expressed in sevoflurane anesthetized tissues at the same time, especially in M1 phenotypes (P<0.01). The polarization of macrophages in the anesthetic group showed the high level of M1 mRNA, and the expression levels of TNF-α, monocyte chemotactic protein 1(MCP-1) and Interleukin-6 (IL-6)mRNA in the anesthetic group were significantly higher than those in the control group (P<0.05). The expression levels of M2 mRNA such as transforming growth factor-β (TGF-β) and IL-10 were significantly lower than those in the control group (P<0.05). Compared with the control group, the expression of FoxO1 and p21 protein in the anesthesia group was significantly lower than that in the control group with a significant statistical difference (P<0.01). Conclusion: This study offers a theoretical basis and insight for further understanding of the prevention and treatment of cognitive dysfunction induced by anesthetic drugs.


2021 ◽  
pp. 159101992110399
Author(s):  
Daizo Ishii ◽  
Mario Zanaty ◽  
Jorge A Roa ◽  
Luyuan Li ◽  
Yongjun Lu ◽  
...  

Objective Post operative cognitive dysfunction (POCD) has been widely observed after major surgery, particularly in elderly patients with general anesthesia (GA). However, a specific unanswered question is whether different approaches to anesthetic managements are associated with different cognitive outcomes after endovascular treatments for unruptured intracranial aneurysms (UIAs). The purpose of this study is to assess the correlation of POCD with GA versus monitored anesthesia care (MAC). Methods We performed a pragmatic, prospective study to assess the association between different anesthetic approaches and POCD. We compared the pre- and post-procedural Montreal Cognitive Assessment (MoCA) scores in patients with normal cognition who underwent treatments of UIAs with various endovascular methods, using either GA or MAC. Results A total of 23 patients with UIAs were enrolled in the study. Seven (30.4%) and sixteen (69.6%) UIAs were treated without perioperative complications under GA or MAC, respectively. There was a significant decline in the post-procedural MoCA score under GA (mean difference  =  1.14; 95% confidence interval  =  [0.42–1.87], P < 0.01). By contrast, there was no significant difference of MoCA score between pre- and post-procedure under MAC (mean difference  =  0.19; 95% confidence interval  =  [−0.29–0.67], P  =  0.59). Conclusions Treating UIAs using MAC was associated with a decrease in POCD as compared to GA in patients undergoing endovascular treatments for UIAs with normal cognition. Larger randomized studies are needed to confirm these findings.


Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 727
Author(s):  
Lingli Gui ◽  
Zhen Luo ◽  
Weiran Shan ◽  
Zhiyi Zuo

Postoperative cognitive dysfunction (POCD) is a significant clinical issue. Its neuropathogenesis has not been clearly identified and effective interventions for clinical use to reduce POCD have not been established. This study was designed to determine whether environmental enrichment (EE) or cognitive enrichment (CE) reduces POCD and whether sex-determining region Y-box-2 regulated by sirtuin 1, plays a role in the effect. Eighteen-month-old male mice were subjected to right-common-carotid-artery exposure under sevoflurane anesthesia. Some of them stayed in cages with EE or CE after the surgery. Learning and memory of mice were tested by a Barnes maze and fear conditioning, starting 2 weeks after the surgery. Sex-determining region Y-box-2 (Sox2) in the brain was silenced by small hairpin RNA (shRNA). Immunofluorescent staining was used to quantify Sox2-positive cells. Surgery reduced Sox2-positive cells in the hippocampus (64 ± 9 cells vs. 91 ± 9 cells in control group, n = 6, p < 0.001) and impaired learning and memory (time to identify target box one day after training sessions in the Barnes maze test: 132 ± 53 s vs. 79 ± 53 s in control group, n = 10, p = 0.040). EE or CE applied after surgery attenuated this reduction of Sox2 cells and POCD. Surgery reduced sirtuin 1 activity and CE attenuated this reduction. Resveratrol, a sirtuin 1 activator, attenuated POCD and surgery-induced decrease of Sox2-positive cells. Silencing shRNA reduced the Sox2-positive cells in the hippocampus and impaired learning and memory in mice without surgery. These results suggest a role of Sox2 in learning, memory, and POCD. EE and CE attenuated POCD via maintaining Sox2-positive cells in the hippocampus.


2016 ◽  
Vol 124 (2) ◽  
pp. 353-361 ◽  
Author(s):  
Lisbeth Evered ◽  
Brendan Silbert ◽  
David A. Scott ◽  
David Ames ◽  
Paul Maruff ◽  
...  

Abstract Background Postoperative cognitive dysfunction (POCD) affects 16 to 21% of the elderly 3 months after anesthesia and surgery and is associated with adverse outcomes. The exact cause of POCD remains unknown. The authors hypothesized that elderly individuals with Alzheimer disease (AD) neuropathology, identified by cerebrospinal fluid (CSF) analysis, would have increased the risk for POCD. Methods CSF samples were collected from 59 patients 60 yr or older who received combined spinal and general anesthesia for elective total hip replacement. Patients underwent neuropsychological testing preoperatively and at 7 days, 3 months, and 12 months postoperatively. POCD at 3 months and cognitive decline at 12 months were calculated by using the reliable change index. CSF amyloid β1–42 (Aβ1–42), total-tau, phosphorylated-tau, and neurofilament light were assayed with enzyme-linked immunosorbent assay methods. Results POCD was identified in 5 of 57 patients (8.8%) at 3 months. For Aβ1–42, 11 patients were below the cut-point for AD neuropathology of whom 3 were classified with POCD (27.3%; 95% CI, 6.0 to 61%), whereas of the 46 patients above the cut-point, 2 were classified with POCD (4.3%; 95% CI, 0.5 to 14.8%) (P = 0.01). There was no significant difference in the incidence of POCD in relation to the cut-points for any of the other analytes. Conclusions Low CSF Aβ1–42 may be a significant predictor of POCD at 3 months. This indicates that patients with AD neuropathology even in the absence of clinically detectable AD symptoms may be susceptible to POCD.


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