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Inflammasome links traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease

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Neural Regeneration Research 2025年第6期20卷 1644-1664页

作者： Gabriela Seplovich Yazan Bouchi Juan Pablo de Rivero Vaccari Jennifer C.Munoz Pareja Andrew Reisner Laura Blackwell Yehia Mechref Kevin K.Wang J.Adrian Tyndall Binu Tharakan Firas Kobeissy department of Surgery Morehouse School of MedicineAtlantaGAUSA department of Neurobiology Center for NeurotraumaMultiomics&Biomarkers(CNMB)Neuroscience InstituteMorehouse School of MedicineAtlantaGAUSA department of Neurological Surgery and the Miami Project to Cure Paralysis University of Miami Miller School of MedicineMiamiFLUSA Division of pediatric critical care Department of PediatricsUniversity of Miami Miller School of MedicineMiamiFLUSA department of pediatrics Emory UniversityAtlantaGAUSA department of Neurosurgery Children’s Healthcare of AtlantaAtlantaGAUSA department of Chemistry and Biochemistry Texas Tech UniversityLubbockTXUSA Morehouse School of Medicine AtlantaGAUSA

Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease are three distinct neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. One sequela of neuroinflammation includes the pathologic hyperphosphorylation of tau protein, an endogenous microtubule-associated protein that protects the integrity of neuronal cytoskeletons. Tau hyperphosphorylation results in protein misfolding and subsequent accumulation of tau tangles forming neurotoxic aggregates. These misfolded proteins are characteristic of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease and can lead to downstream neuroinflammatory processes, including assembly and activation of the inflammasome complex. Inflammasomes refer to a family of multimeric protein units that, upon activation, release a cascade of signaling molecules resulting in caspase-induced cell death and inflammation mediated by the release of interleukin-1β cytokine. One specific inflammasome, the NOD-like receptor protein 3, has been proposed to be a key regulator of tau phosphorylation where it has been shown that prolonged NOD-like receptor protein 3 activation acts as a causal factor in pathological tau accumulation and spreading. This review begins by describing the epidemiology and pathophysiology of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease. Next, we highlight neuroinflammation as an overriding theme and discuss the role of the NOD-like receptor protein 3 inflammasome in the formation of tau deposits and how such tauopathic entities spread throughout the brain. We then propose a novel framework linking traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease as inflammasomedependent pathologies that exist along a temporal continuum. Finally, we discuss potential therapeutic targets that may intercept this pathway and ultimately minimize long-term neurological decline.

关键词： Alzheimer's disease caspase-1 chronic traumatic encephalopathy inflammasomes neurodegeneration neuroinflammation NLRP1 NLRP3 pyroptosis tauopathy traumatic brain injury

High-dose dexamethasone regulates microglial polarization via the GR/JAK1/STAT3 signaling pathway after traumatic brain injury

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Neural Regeneration Research 2025年第9期20卷 2611-2623页

作者： Mengshi Yang Miao Bai Yuan Zhuang Shenghua Lu Qianqian Ge Hao Li Yu Deng Hongbin Wu Xiaojian Xu Fei Niu Xinlong Dong Bin Zhang Baiyun Liu Beijing Tiantan Hospital Capital Medical UniversityBeijingChina department of Neurology The First Hospital of Tsinghua UniversityBeijingChina department of Neurotrauma and Beijing Key Laboratory of Central Nervous System Injury Beijing Neurosurgical InstituteCapital Medical UniversityBeijingChina department of critical care Medicine Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Center for Nerve Injury and Repair Beijing Institute of Brain DisordersChina National Clinical Research Center for Neurological DiseasesBeijingChina

Although microglial polarization and neuroinflammation are crucial cellular responses after traumatic brain injury,the fundamental regulatory and functional mechanisms remain insufficiently *** potent anti-inflammato ry agents,the use of glucoco rticoids in traumatic brain injury is still controversial,and their regulatory effects on microglial polarization are not yet *** the present study,we sought to determine whether exacerbation of traumatic brain injury caused by high-dose dexamethasone is related to its regulatory effects on microglial polarization and its mechanisms of *** vitro cultured BV2 cells and primary microglia and a controlled cortical impact mouse model were used to investigate the effects of dexamethasone on microglial ***,dexamethasone,RU486(a glucocorticoid receptor antagonist),and ruxolitinib(a Janus kinase 1 antagonist)were ***-sequencing data obtained from a C57BL/6 mouse model of traumatic brain injury were used to identify potential targets of *** Morris water maze,quantitative reverse transcription-polymerase chain reaction,western blotting,immunofluorescence and confocal microscopy analysis,and TUNEL,Nissl,and Golgi staining were performed to investigate our ***-throughput sequencing results showed that arginase 1,a marker of M2 microglia,was significantly downregulated in the dexamethasone group compared with the traumatic brain injury group at3 days post-traumatic brain *** dexamethasone inhibited M1 and M2 microglia,with a more pronounced inhibitory effect on M2microglia in vitro and in *** receptor plays an indispensable role in microglial polarization after dexamethasone treatment following traumatic brain ***,glucocorticoid receptor activation increased the number of apoptotic cells and neuronal death,and also decreased the density of dendritic spines.A possible downstream receptor signaling mechanism is th

关键词： apoptosis BV2 microglia dexamethasone glucocorticoid receptor glucocorticoids innate immune system microglial polarization neuroinflammation primary microglia traumatic brain injury

Establishment of a Rat Model of Capillary Leakage Syndrome Induced by Cardiopulmonary Resuscitation After Cardiac Arrest

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Current Medical Science 2023年第4期43卷 708-715页

作者： Xiao-lei ZHANG Ye CHENG Chun-lin XING Jia-yun YING Xue YANG Xiao-di CAI Guo-ping LU department of pediatric Emergency Medicine and critical care Medicine Children's Hospital of Fudan UniversityShanghai 201102China department of pediatric critical care Medicine Children's Hospital of Chongqing Medical UniversityChongqing 400014China

Objective:Cardiopulmonary resuscitation(CPR)after cardiac arrest(CA)is one of the main causes of capillary leakage syndrome(CLS).This study aimed to establish a stable CLS model following the CA and cardiopulmonary resuscitation(CA-CPR)model in Sprague-Dawley(SD)***:We conducted a prospective,randomized,animal model *** adult male SD rats were randomly divided into a normal group(group N),a sham operation group(group S),and a cardiopulmonary resuscitation group(group T).The SD rats of the three groups were all inserted with 24-G needles through their left femoral arteries and right femoral *** group S and group T,the endotracheal tube was *** group T,CA induced by asphyxia(AACA)was caused by vecuronium bromide with the endotracheal tube obstructed for 8 min,and the rats were resuscitated with manual chest compression and mechanical *** and postresuscitation measurements,including basic vital signs(BVS),blood gas analysis(BG),routine complete blood count(CBC),wet-to-dry ratio of tissues(W/D),and the HE staining results after 6 h were ***:In group T,the success rate of the CA-CPR model was 60%(18/30),and CLS occurred in 26.6%(8/30)of the *** were no significant differences in the baseline characteristics,including BVS,BG,and CBC,among the three groups(P>0.05).Compared with pre-asphyxia,there were significant differences in BVS,CBC,and BG,including temperature,oxygen saturation(SpO_(2)),mean arterial pressure(MAP),central venous pressure(CVP),white blood cell count(WBC),hemoglobin,hematocrit,pH,pCO_(2),pO_(2),SO_(2),lactate(Lac),base excess(BE),and Na+(P<0.05)after the return of spontaneous circulation(ROSC)in group *** 6 h after ROSC in group T and at 6 h after surgery in groups N and S,there were significant differences in temperature,heart rate(HR),respiratory rate(RR),SpO_(2),MAP,CVP,WBC,pH,pCO_(2),Na+,and K+among the three groups(P<0.05).Compared with the other two groups,the rats in group

关键词： cardiac arrest cardiopulmonary resuscitation capillary leakage model

Protein-mediated interactions in the dynamic regulation of acute inflammation

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BIOCELL 2023年第6期47卷 1191-1198页

作者： RYAN STARK department of pediatric critical care Medicine Vanderbilt University Medical CenterNashvilleTN37232-9075USA

Protein-mediated interactions are the fundamental mechanism through which cells regulate health and *** interactions require physical contact between proteins and their respective targets of *** targets include not only other proteins but also nucleic acids and other important molecules as *** proteins are often involved in multibody complexes that work dynamically to regulate cellular health and *** techniques have been adapted to study these important interactions,such as affinity-based assays,mass spectrometry,and fluorescent *** application of these techniques has led to a greater understanding of how protein interactions are responsible for both the instigation and resolution of acute inflammatory *** pursuits aim to provide opportunities to target specific protein interactions to alleviate acute inflammation.

关键词： Protein interactions Inflammation Sepsis RNA DNA Therapeutics

Spatial transcriptomics combined with single-nucleus RNA sequencing reveals glial cell heterogeneity in the human spinal cord

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Neural Regeneration Research 2025年第11期20卷 3302-3316页

作者： Yali Chen Yiyong Wei Jin Liu Tao Zhu Cheng Zhou Donghang Zhang department of Anesthesiology West China HospitalSichuan UniversityChengduSichuan ProvinceChina Laboratory of Anesthesia and critical care Medicine National-Local Joint Engineering Research Center of Translational Medicine of AnesthesiologyWest China HospitalSichuan UniversityChengduSichuan ProvinceChina department of Anesthesiology Longgang District Maternity&Child Healthcare Hospital of Shenzhen City(Longgang Maternity and Child Institute of Shantou University Medical College)ShenzhenGuangdong ProvinceChina department of Anesthesiology Affiliated Hospital of Zunyi Medical UniversityZunyiGuizhou ProvinceChina

Glial cells play crucial roles in regulating physiological and pathological functions,including sensation,the response to infection and acute injury,and chronic neurodegenerative *** cells include astrocytes,microglia,and oligodendrocytes in the central nervous system,and satellite glial cells and Schwann cells in the peripheral nervous *** the greater understanding of glial cell types and functional heterogeneity achieved through single-cell and single-nucleus RNA sequencing in animal models,few studies have investigated the transcriptomic profiles of glial cells in the human spinal ***,we used high-throughput single-nucleus RNA sequencing and spatial transcriptomics to map the cellular and molecular heterogeneity of astrocytes,microglia,and oligodendrocytes in the human spinal *** explore the conservation and divergence across species,we compared these findings with those from *** the human spinal cord,astrocytes,microglia,and oligodendrocytes were each divided into six distinct transcriptomic *** the mouse spinal cord,astrocytes,microglia,and oligodendrocytes were divided into five,four,and five distinct transcriptomic subclusters,*** comparative results revealed substantial heterogeneity in all glial cell types between humans and ***,we detected sex differences in gene expression in human spinal cord glial ***,in all astrocyte subtypes,the levels of NEAT1 and CHI3L1 were higher in males than in females,whereas the levels of CST3 were lower in males than in *** all microglial subtypes,all differentially expressed genes were located on the sex *** addition to sex-specific gene differences,the levels of MT-ND4,MT2A,MT-ATP6,MT-CO3,MT-ND2,MT-ND3,and MT-CO_(2) in all spinal cord oligodendrocyte subtypes were higher in females than in ***,the present dataset extensively characterizes glial cell heterogeneity and offers a valuable resource for explo

关键词： astrocyte glial cell human microglia oligodendrocyte sex differentiation single-nucleus RNA sequencing spatial transcriptomics species variation spinal cord

Eosinophils in asthma

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Chinese Medical Journal 2004年第5期117卷 792-794页

作者：施焕中 department of Pulmonary and critical care Medicine

The contribution of eosinophils to host-defense and inflammatory responses has undergone periodic reevalu-ations. Thirty years ago, eosinophil was considered as a principal effector cell in host-defense against parasi... 详细信息

关键词： IL SCH Eosinophils in asthma

EZH2-dependent myelination following sciatic nerve injury

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Neural Regeneration Research 2025年第8期20卷 2382-2394页

作者： Hui Zhu Li Mu Xi Xu Tianyi Huang Ying Wang Siyuan Xu Yiting Wang Wencong Wang Zhiping Wang Hongkui Wang Chengbin Xue Research Center of Clinical Medicine Affiliated Hospital of Nantong UniversityKey Laboratory of Neuroregeneration of Jiangsu and Ministry of EducationCo-innovation Center of NeuroregenerationNMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology ProductsNantong UniversityNantongJiangsu ProvinceChina Medical School of Nantong University NantongJiangsu ProvinceChina department of Neurology Affiliated Hospital of Nantong UniversityNantongJiangsu ProvinceChina department of Rehabilitation Medicine Affiliated Hospital of Nantong UniversityNantongJiangsu ProvinceChina department of critical care Medicine Nantong Fourth People’s HospitalNantongJiangsu ProvinceChina

Demyelination and remyelination have been major focal points in the study of peripheral nerve regeneration following peripheral nerve ***,the gene regulatory network of regenerated myelin differs from that of native *** of enhancer of zeste homolog 2(EZH2)hinders the differentiation,maturation,and myelination of Schwann cells in *** further determine the role of EZH2 in myelination and recovery post-peripheral nerve injury,conditional knockout mice lacking Ezh2 in Schwann cells(Ezh2^(fl/fl);Dhh-Cre and Ezh2^(fl/fl);Mpz-Cre)were *** results show that a significant proportion of axons in the sciatic nerve of Ezh2-depleted mice remain *** highlights the crucial role of Ezh2 in initiating Schwann cell ***,we observed that 21 days after inducing a sciatic nerve crush injury in these mice,most axons had remyelinated at the injury site in the control nerve,while Ezh2^(fl/fl);Mpz-Cre mice had significantly fewer remyelinated axons compared with their wild-type *** suggests that the absence of Ezh2 in Schwann cells impairs myelin formation and *** conclusion,EZH2 has emerged as a pivotal regulatory factor in the process of demyelination and myelin regeneration following peripheral nerve *** EZH2 activity during these processes may offer a promising therapeutic target for the treatment of peripheral nerve injuries.

关键词： demyelination EZH2 myelination peripheral nerve injury PRC2 remyelination Schwann cells sciatic nerve crush sciatic nerve transection

Are incidence and severity of clubfoot related to the season of birth?

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World Journal of pediatrics 2016年第3期12卷 360-363页

作者： Da-Hang Zhao Wei-Wei Rao Li Zhao Xuan Yang Jian-Lin Liu Zhen-Kai Wu Qing Du Xiao-Yan Yang department of pediatric Orthopedics department of pediatric critical care Medicine department of Rehabilitation Medicine Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghai 200092China

Background:This study was designed to determine whether the occurrence of clubfoot follows a seasonal pattern in neonates from eastern and south-eastern China and to speculate the potential etiology of ***:We reviewed 239 neonates with clubfeet during a period of 4 years as well as the monthly neonatal population of the Sixth National Population *** variations in terms of month of birth and severity were ***:The incidence of clubfoot in neonates from eastern and south-eastern China showed seasonal variations,and the incidence was higher in autumn with a reference to the average birth rate in this corresponding *** signifi cant difference was found in severity of ***:This seasonal pattern is of signifi cant value to further understanding the etiology and pathogenesis of clubfoot in the corresponding area of China.

关键词： clubfoot etiology seasonality

Performance of the PRISM I,PIM2,PELOD-2 and PRISM IV scoring systems in western China:a multicenter prospective study

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World Journal of pediatrics 2022年第12期18卷 818-824页

作者： Xue-Peng Zhang Yun-Xia Feng Yang Li Guo-Yan Lu Xin-Yue Zhou Can-Zheng Wei Xi-Ying Gui Kai-Ying Yang Tong Qiu Jiang-Yuan Zhou Hua Yao Geng Zhang Wen-Qi Zhang Yu-Hang Hu Hong Wu Si-Yuan Chen Yi Ji department of pediatric Surgery West China Hospital of Sichuan UniversityChengdu610041China department of critical care Medicine West China Hospital of Sichuan UniversityChengdu610041China department of Nephrology Mianyang Central HospitalUniversity of Electronic Science and Technology of ChinaMianyang621000China department of pediatric critical care Medicine West China Women’s and Children’s HospitalSichuan UniversityChengdu610041China department of pediatric critical care Medicine Sichuan Provincial Maternity and Child Health Care HospitalChengdu610041China department of critical care Medicine People’s Hospital of Tibet Autonomous RegionLhasa850000China department of Anesthesiology the Affiliated Hospital of Guizhou Medical UniversityGuiyang550001China department of critical care Medicine Mianyang Central HospitalUniversity of Electronic Science and Technology of ChinaMianyang621000China

Background The aim of this study was to evaluate the performance of the four scoring tools in predicting mortality in pediatric intensive care units(PICUs)in western *** This was a multicenter,prospective,cohort study conducted in six PICUs in western *** performances of the scoring systems were evaluated based on both discrimination and *** was assessed by calculating the area under the receiver operating characteristic curve(AUC)for each *** was measured across defined groups based on mortality risk using the Hosmer-Lemeshow goodness-of-fit *** A total of 2034 patients were included in this study,of whom 127(6.2%)*** the entire cohort,AUCs for pediatric Risk of Mortality Score(PRISM)I,pediatric Index of Mortality 2(PIM2),pediatric Logistic Organ Dysfunction Score-2(PELOD-2)and PRISM IV were 0.88[95%confidence interval(CI)0.85–0.92],0.84(95%CI 0.80–0.88),0.80(95%CI 0.75–0.85),and 0.91(95%CI 0.88–0.94),*** Hosmer-Lemeshow goodness-of-fit Chi-square value was 12.71(P=0.12)for PRISM I,4.70(P=0.79)for PIM2,205.98(P<0.001)for PELOD-2,and 7.50(P=0.48)for PRISM IV[degree of freedom(df)=8].The standardized mortality ratios obtained with the PRISM I,PIM2,PELOD-2,and PRISM IV models were 0.87(95%CI,0.75–1.01),0.97(95%CI,0.85–1.12),1.74(95%CI,1.58–1.92),and 1.05(95%CI,0.92–1.21),*** PRISM IV performed best and can be used as a prediction tool in PICUs in Western ***,PRISM IV needs to be further validated in NICUs.

关键词： Illness severity score Intensive care Mortality prediction pediatric