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General anesthetic agents induce neurotoxicity through astrocytes

Neural Regeneration Research 2024年第6期19卷 1299-1307页

作者： Yanchang Yang Tiantian Liu Jun Li Dandan Yan Yuhan Hu Pin Wu Fuquan Fang Patrick M.McQuillan Wenxin Hang Jianhang Leng Zhiyong Hu department of anesthesiology The First Affiliated Hospital Zhejiang University School of Medicine department of anesthesiology Ningbo Women and Children's Hospital 3. Department of Anesthesiology Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College 4. Cell Biology Department Yale University 5. Department of Anesthesiology Penn State Hershey Medical Centre Penn State College of Medicine 6. Department of Central Laboratory Affiliated Hangzhou First People's Hospital Zhejiang University School of Medicine

Neuroscientists have recognized the importance of astrocytes in regulating neurological function and their influence on the release of glial transmitters. Few studies, however, have focused on the effects of general anesthetic agents on neuroglia or astrocytes. Astrocytes can also be an important target of general anesthetic agents as they exert not only sedative, analgesic, and amnesic effects but also mediate general anesthetic-induced neurotoxicity and postoperative cognitive dysfunction. Here, we analyzed recent advances in understanding the mechanism of general anesthetic agents on astrocytes, and found that exposure to general anesthetic agents will destroy the morphology and proliferation of astrocytes, in addition to acting on the receptors on their surface, which not only affect Ca2+signaling, inhibit the release of brain-derived neurotrophic factor and lactate from astrocytes, but are even involved in the regulation of the pro-and anti-inflammatory processes of astrocytes. These would obviously affect the communication between astrocytes as well as between astrocytes and neighboring neurons, other neuroglia, and vascular cells. In this review, we summarize how general anesthetic agents act on neurons via astrocytes, and explore potential mechanisms of action of general anesthetic agents on the nervous system. We hope that this review will provide a new direction for mitigating the neurotoxicity of general anesthetic agents.

关键词： astrocytes brain-derived neurotrophic factor general anesthetic agents N-methyl-D-aspartate receptor neuron neurotoxicity perioperative neurocognition Toll-like receptor γ-aminobutyric acid receptor

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Effects of sevoflurane on left ventricular function by speckletracking echocardiography in coronary bypass patients: A randomized trial

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The Journal of Biomedical Research 2024年第1期38卷 76-86页

作者： Chanjuan Gong Xiaokai Zhou Yin Fang Yanjuan Zhang Linjia Zhu Zhengnian Ding department of anesthesiology and Perioperative Medicine the First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsu 210029China department of Cardiology the First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsu 210029China.

The present study aimed to dynamically observe the segmental and global myocardial movements of the left ventricle during coronary artery bypass grafting by transesophageal speckle-tracking echocardiography,and to assess the effect of sevoflurane on cardiac function.Sixty-four patients scheduled for the off-pump coronary artery bypass grafting were randomly divided into a sevoflurane-based anesthesia(AS)group and a propofolbased total intravenous anesthesia(AA)group.The AS group demonstrated a higher absolute value of left ventricular global longitudinal strain than that of the AA group at both T1(after harvesting all grafts and before coronary anastomosis)and T_(2)(30 min after completing all coronary anastomoses)(P<0.05).Moreover,strain improvement in the segment with the highest preoperative strain was significantly reduced in the AS group,compared with the AA group at both T1 and T_(2)(P<0.01).The flow of the left internal mammary artery-left anterior descending artery graft was superior,and the postoperative concentration of troponin T decreased rapidly in the AS group,compared with the AA group(P<0.05).Compared with total intravenous anesthesia,sevoflurane resulted in a significantly higher global longitudinal strain,stroke volume,and cardiac output.Sevoflurane also led to an amelioration in the condition of the arterial graft.Furthermore,sevoflurane significantly reduced strain improvement in the segmental myocardium with a high preoperative strain value.The findings need to be replicated in larger studies.

关键词： coronary artery bypass grafting speckle-tracking echocardiography sevoflurane transesophageal echocardiography

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Mitochondrial transplantation confers protection against the effects of ischemic stroke by repressing microglial pyroptosis and promoting neurogenesis

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Neural Regeneration Research 2024年第6期19卷 1325-1335页

作者： Li Sun Zhaoyan Zhao Jing Guo Yuan Qin Qian Yu Xiaolong Shi Fei Guo Haiqin Zhang Xude Sun Changjun Gao Qian Yang department of Experimental Surgery The Second Affiliated Hospital of Air Force Medical University department of anesthesiology The Second Affiliated Hospital of Air Force Medical University

Transferring healthy and functional mitochondria to the lateral ventricles confers neuroprotection in a rat model of ischemia-reperfusion injury. Autologous mitochondrial transplantation is also beneficial in pediatric patients with cardiac ischemia-reperfusion injury. Thus, transplantation of functional exogenous mitochondria may be a promising therapeutic approach for ischemic disease. To explore the neuroprotective effect of mitochondria transplantation and determine the underlying mechanism in ischemic stroke, in this study we established a photo-thrombosis-induced mouse model of focal ischemia and administered freshly isolated mitochondria via the tail vein or to the injury site(in situ). Animal behavior tests, immunofluorescence staining, 2,3,5-triphenyltetrazolium chloride(TTC) staining, mRNA-seq, and western blotting were used to assess mouse anxiety and memory, cortical infarct area, pyroptosis, and neurogenesis, respectively. Using bioinformatics analysis, western blotting, co-immunoprecipitation, and mass spectroscopy, we identified S100 calcium binding protein A9(S100A9) as a potential regulator of mitochondrial function and determined its possible interacting proteins. Interactions between exogenous and endogenous mitochondria, as well as the effect of exogenous mitochondria on recipient microglia, were assessed in vitro. Our data showed that:(1) mitochondrial transplantation markedly reduced mortality and improved emotional and cognitive function, as well as reducing infarct area, inhibiting pyroptosis, and promoting cortical neurogenesis;(2) microglial expression of S100A9 was markedly increased by ischemic injury and regulated mitochondrial function;(3) in vitro, exogenous mitochondria enhanced mitochondrial function, reduced redox stress, and regulated microglial polarization and pyroptosis by fusing with endogenous mitochondria; and(4) S100A9 promoted internalization of exogenous mitochondria by the microglia, thereby amplifying their pro-proliferation and anti-inflammatory effects. Taken togeth

关键词： ischemic stroke microglia mitochondria transplantation neurogenesis pyroptosis

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Evaluating the use of three-dimensional reconstruction visualization technology for precise laparoscopic resection in gastroesophageal junction cancer

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World Journal of Gastrointestinal Surgery 2024年第5期16卷 1311-1319页

作者： Dan Guo Xiao-Yan Zhu Shuai Han Yu-Shu Liu Da-Peng Cui department of Hepatobiliary Surgery The First Affiliated Hospital of Hebei North UniversityZhangjiakou 075000Hebei ProvinceChina department of anesthesiology The First Affiliated Hospital of Hebei North UniversityZhangjiakou 075000Hebei ProvinceChina

BACKGROUND Laparoscopic gastrectomy for esophagogastric junction(EGJ)carcinoma enables the removal of the carcinoma at the junction between the stomach and esophagus while preserving the gastric function,thereby providing patients with better treatment outcomes and quality of life.Nonetheless,this surgical technique also presents some challenges and limitations.Therefore,three-dimensional reconstruction visualization technology(3D RVT)has been introduced into the procedure,providing doctors with more comprehensive and intuitive anatomical information that helps with surgical planning,navigation,and outcome evaluation.AIM To discuss the application and advantages of 3D RVT in precise laparoscopic resection of EGJ carcinomas.METHODS Data were obtained from the electronic or paper-based medical records at The first affiliated hospital of Hebei North University from January 2020 to June 2022.A total of 120 patients diagnosed with EGJ carcinoma were included in the study.Of these,68 underwent laparoscopic resection after computed tomography(CT)-enhanced scanning and were categorized into the 2D group,whereas 52 underwent laparoscopic resection after CT-enhanced scanning and 3D RVT and were categorized into the 3D group.This study had two outcome measures:the deviation between tumor-related factors(such as maximum tumor diameter and infiltration length)in 3D RVT and clinical reality,and surgical outcome indicators(such as operative time,intraoperative blood loss,number of lymph node dissections,R0 resection rate,postoperative hospital stay,postoperative gas discharge time,drainage tube removal time,and related complications)between the 2D and 3D groups.RESULTS Among patients included in the 3D group,27 had a maximum tumor diameter of less than 3 cm,whereas 25 had a diameter of 3 cm or more.In actual surgical observations,24 had a diameter of less than 3 cm,whereas 28 had a diameter of 3 cm or more.The findings were consistent between the two methods(χ^(2)=0.346,P=0.556),with a kappa consistency coefficient of 0.808.Wit

关键词： Gastroesophageal junction cancer Endoscopy Tumor resection Three-dimensional reconstruction visualization Two-dimensional imaging computed tomography

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In vivo imaging reveals a synchronized correlation among neurotransmitter dynamics during propofol and sevoflurane anesthesia

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Zoological Research 2024年第3期45卷 679-690页

作者： Gao-Lin Qiu Li-Jun Peng Peng Wang Zhi-Lai Yang Ji-Qian Zhang Hu Liu Xiao-Na Zhu Jin Rao Xue-Sheng Liu department of anesthesiology First Affiliated Hospital of Anhui Medical UniversityHefeiAnhui 230022China School of Life Science and Technology ShanghaiTech UniversityShanghai 201210China

General anesthesia is widely applied in clinical practice.However,the precise mechanism of loss of consciousness induced by general anesthetics remains unknown.Here,we measured the dynamics of five neurotransmitters,includingγ-aminobutyric acid,glutamate,norepinephrine,acetylcholine,and dopamine,in the medial prefrontal cortex and primary visual cortex of C57BL/6 mice through in vivo fiber photometry and genetically encoded neurotransmitter sensors under anesthesia to reveal the mechanism of general anesthesia from a neurotransmitter perspective.Results revealed that the concentrations of γ-aminobutyric acid,glutamate,norepinephrine,and acetylcholine increased in the cortex during propofol-induced loss of consciousness.Dopamine levels did not change following the hypnotic dose of propofol but increased significantly following surgical doses of propofol anesthesia.Notably,the concentrations of the five neurotransmitters generally decreased during sevoflurane-induced loss of consciousness.Furthermore,the neurotransmitter dynamic networks were not synchronized in the non-anesthesia groups but were highly synchronized in the anesthetic groups.These findings suggest that neurotransmitter dynamic network synchronization may cause anesthetic-induced loss of consciousness.

关键词： General anesthesia Loss of consciousness In vivo neurotransmitter imaging Medial prefrontal cortex Primary visual cortex

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Fibroblast growth factor 21 inhibits ferroptosis following spinal cord injury by regulating heme oxygenase-1

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Neural Regeneration Research 2024年第7期19卷 1568-1574页

作者： Qi Gu Weiping Sha Qun Huang Jin Wang Yi Zhu Tianli Xu Zhenhua Xu Qiancheng Zhu Jianfei Ge Shoujin Tian Xiaolong Lin department of Orthopaedic Surgery Zhangjiagang Hospital Affiliated to Soochow UniversitySuzhouJiangsu ProvinceChina Orthopedics Laboratory The First People’s Hospital of Zhangjiagang CitySuzhouJiangsu ProvinceChina department of anesthesiology Zhangjiagang Hospital Affiliated to Soochow UniversitySuzhouJiangsu ProvinceChina

Interfering with the ferroptosis pathway is a new strategy for the treatment of spinal cord injury.Fibroblast growth factor 21 can inhibit ferro ptosis and promote neurofunctional recovery,while heme oxygenase-1 is a regulator of iron and reactive oxygen species homeostasis.The relationship between heme oxygenase-1and ferroptosis remains controve rsial.In this study,we used a spinal co rd injury rat model to show that the levels of fibroblast growth factor 21 in spinal co rd tissue decreased after spinal cord injury.In addition,there was a significant aggravation of ferroptosis and a rapid increase in heme oxygenase-1 expression after spinal cord injury.Furthe r,heme oxygenase-1 aggravated fe rroptosis after spinal cord injury,while fibroblast growth factor 21 inhibited fe rroptosis by downregulating heme oxygenase-1.Thus,the activation of fibroblast growth factor 21 may provide a potential treatment for spinal co rd injury.These findings could provide a new potential mechanistic explanation for fibroblast growth factor 21 in the treatment of spinal cord injury.

关键词： ferroptosis fibroblast growth factor 21 functional recovery heme oxygenase-1 lipid peroxidation neuron reactive oxygen species spinal cord injury

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Effect of remimazolam vs. propofol on hemodynamics during general anesthesia induction in elderly patients: Single-center, randomized controlled trial

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The Journal of Biomedical Research 2024年第1期38卷 66-75页

作者： Mingfeng He Chanjuan Gong Yinan Chen Rongting Chen Yanning Qian department of anesthesiology and Perioperative Medicine the First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsu 210029China

The current study aimed to compare the effects between remimazolam and propofol on hemodynamic stability during the induction of general anesthesia in elderly patients.We used propofol at a rate of 60 mg/(kg·h)in the propofol group(group P)or remimazolam at a rate of 6 mg/(kg·h)in the remimazolam group(group R)for the induction.A processed electroencephalogram was used to determine whether the induction was successful and when to stop the infusion of the study drug.We measured when patients entered the operating room(T_(0)),when the induction was successful(T_(1)),and when before(T_(2))and 5 min after successful endotracheal intubation(T_(3)).We found that mean arterial pressure(MAP)was lower at T_(1–3),compared with T_(0) in both groups,but higher at T_(2) in the group R,whileΔMAP_(T0–T2) andΔMAP_(max) were smaller in the group R(ΔMAP_(T0–T2):the difference between MAP at time point T_(0) and T_(2),ΔMAP_(max):the difference between MAP at time point T_(0) and the lowest value from T_(0) to T_(3)).Cardiac index and stroke volume index did not differ between groups,whereas systemic vascular resistance index was higher at T_(1–3) in the group R.These findings show that remimazolam,compared with propofol,better maintains hemodynamic stability during the induction,which may be attributed to its ability to better maintain systemic vascular resistance levels.

关键词： remimazolam propofol elderly patients hypotension left ventricular systolic function systematic vascular resistance

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Efficacy and safety of remimazolam in bronchoscopic sedation:A meta-analysis

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World Journal of Clinical Cases 2024年第6期12卷 1120-1129页

作者： Ying Zhou Cheng Zhao Yi-Xun Tang Ji-Tong Liu department of anesthesiology The First Affiliated Hospital of Hunan Normal University(Hunan Provincial People’s Hospital)Changsha 410005Hunan ProvinceChina department of anesthesiology Zhangjiajie People's HospitalZhangjiajie 427000Hunan ProvinceChina

BACKGROUND Remimazolam is a new benzodiazepine used for procedural sedation and general anesthesia.Several studies have used remimazolam for bendable bronchoscopy.AIM To assess the safety and efficacy of remimazolam for sedation in patients undergoing bendable bronchoscopy by performing a meta-analysis of randomized controlled trials(RCTs).METHODS We searched the EMBASE,PubMed,Cochrane Library,and Web of Science databases for RCTs on bendable bronchoscopic procedural sedation with remimazolam vs conventional sedatives(CS).RESULTS Five studies with 1080 cases were included.Remimazolam had the same sedation success rate compared with CS[relative risk(RR):1.35,95%CI:0.60-3.05,P=0.474,I2=99.6%].However,remimazolam was associated with a lower incidence of hypotension(RR:0.61;95%CI:0.40-0.95,P=0.027;I2=65.1%)and a lower incidence of respiratory depression(RR:0.50,95%CI:0.33-0.77,P=0.002,I2=42.3%).A subgroup analysis showed a higher success rate of sedation with remimazolam than midazolam(RR:2.45,95%CI:1.76-3.42,P<0.001).Compared with propofol,the incidence of hypotension(RR:0.45,95%CI:0.32-0.64,P<0.001,I2=0.0%),respiratory depression(RR:0.48,95%CI:0.30-0.76,P=0.002,I2=78.4%),hypoxemia(RR:0.36,95%CI:0.15-0.87,P=0.023),and injection pain(RR:0.04,95%CI:0.01-0.28,P=0.001)were lower.CONCLUSION Remimazolam is safe and effective during bronchoscopy.The sedation success rate was similar to that in the CS group.However,remimazolam has a higher safety profile,with fewer inhibitory effects on respiration and circulation.

关键词： Remimazolam Bronchoscopy Procedural sedation Meta-analysis

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Safety and efficacy comparison of remimazolam and propofol for intravenous anesthesia during gastroenteroscopic surgery of older patients:A meta-analysis

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World Journal of Clinical Cases 2024年第7期12卷 1272-1283页

作者： Fang-Zhuo Li Cheng Zhao Yi-Xun Tang Ji-Tong Liu department of anesthesiology The First Affiliated Hospital of Hunan Normal University(Hunan Provincial People’s Hospital)Changsha 410005Hunan ProvinceChina department of anesthesiology Zhangjiajie People's HospitalZhangjiajie 427000Hunan ProvinceChina

BACKGROUND Remimazolam is characterized by rapid action and inactive metabolites.It is used as the general anesthetic for many clinical surgeries.In this study,we performed a meta-analysis to evaluate whether remimazolam is superior to propofol for gastroenteroscopy in older patients.AIM To compare the adverse events and efficacy of remimazolam and propofol during gastroenteroscopy in older adults.METHODS The PubMed,Web of Science,the Cochrane Library databases were queried for the relevant key words"remimazolam,""and propofol,""and gastrointestinal endoscopy or gastroscopy."The search scope was"Title and Abstract,"and the search was limited to human studies and publications in English.Seven studies wherein remimazolam and propofol were compared were included for the metaanalysis.RESULTS We selected seven randomized controlled trials involving 1445 cases for the analysis.Remimazolam reduced the hypotension(relative risk,RR=0.44,95%CI:0.29-0.66,P=0.000),respiratory depression(RR=0.46,95%CI:0.30-0.70,P=0.000),injection pain(RR=0.12,95%CI:0.05-0.25,P=0.000),bradycardia(RR=0.37,95%CI:0.24-0.58,P=0.000),and time to discharge[weighted mean difference(WMD)=-0.58,95%CI:-0.97 to-0.18,P=0.005],compared to those after propofol administration.No obvious differences were observed for postoperative nausea and vomiting(RR=1.09,95%CI:0.97-1.24,P=0.151),dizziness(RR=0.77,95%CI:0.43-1.36,P=0.361),successful sedation rate(RR=0.96,95%CI:0.93-1.00,P=0.083),or the time to become fully alert(WMD=0.00,95%CI:-1.08-1.08,P=0.998).CONCLUSION Remimazolam appears to be safer than propofol for gastroenteroscopy in older adults.However,further studies are required to confirm these findings.

关键词： Remimazolam Propofol Gastroenteroscopy Anesthesia Older adults Sedation Adverse events

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Cav3.2 channel regulates cerebral ischemia/reperfusion injury:a promising target for intervention

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Neural Regeneration Research 2024年第11期19卷 2480-2487页

作者： Feibiao Dai Chengyun Hu Xue Li Zhetao Zhang Hongtao Wang Wanjun Zhou Jiawu Wang Qingtian Geng Yongfei Dong Chaoliang Tang Graduate School Wannan Medical CollegeWuhuAnhui ProvinceChina department of anesthesiology The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui ProvinceChina Core Facility Center for Medical Sciences The First Affiliated Hospital of USTC(Anhui Provincial Hospital)HefeiAnhui ProvinceChina department of Pharmacy The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui ProvinceChina department of Neurosurgery The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui ProvinceChina

Calcium influx into neurons triggers neuronal death during cerebral ischemia/reperfusion injury.Various calcium channels are involved in cerebral ischemia/reperfusion injury.Cav3.2 channel is a main subtype of T-type calcium channels.T-type calcium channel blockers,such as pimozide and mibefradil,have been shown to prevent cerebral ischemia/reperfusion injury-induced brain injury.However,the role of Cav3.2 channels in cerebral ischemia/reperfusion injury remains unclear.Here,in vitro and in vivo models of cerebral ischemia/reperfusion injury were established using middle cerebral artery occlusion in mice and high glucose hypoxia/reoxygenation exposure in primary hippocampal neurons.The results showed that Cav3.2 expression was significantly upregulated in injured hippocampal tissue and primary hippocampal neurons.We further established a Cav3.2 gene-knockout mouse model of cerebral ischemia/reperfusion injury.Cav3.2 knockout markedly reduced infarct volume and brain water content,and alleviated neurological dysfunction after cerebral ischemia/reperfusion injury.Additionally,Cav3.2 knockout attenuated cerebral ischemia/reperfusion injury-induced oxidative stress,inflammatory response,and neuronal apoptosis.In the hippocampus of Cav3.2-knockout mice,calcineurin overexpression offset the beneficial effect of Cav3.2 knockout after cerebral ischemia/reperfusion injury.These findings suggest that the neuroprotective function of Cav3.2 knockout is mediated by calcineurin/nuclear factor of activated T cells 3 signaling.Findings from this study suggest that Cav3.2 could be a promising target for treatment of cerebral ischemia/reperfusion injury.

关键词： calcineurin Cav3.2 channel cerebral ischemia/reperfusion hippocampus hypoxia/reoxygenation inflammatory response nuclear factor of activated T cells 3 oxidative stress primary hippocampal neurons stroke

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