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A systematic review of the role of TREM2 in Alzheimer’s disease

中华医学杂志(英文版) 2024年第14期137卷 1684-1694页

作者： Yin Yunsi Yang Hanchen Li Ruiyang Wu Guangshan Qin Qi Tang Yi department of Neurology & Innovation Center for neurological Disorders Xuanwu Hospital Capital Medical University National Center for Neurological Disorders Beijing China

Background: Given the established genetic linkage between triggering receptors expressed on myeloid cells 2 (TREM2) and Alzheimer’s disease (AD), an expanding research body has delved into the intricate role of TREM2 within the AD context. However, a conflicting landscape of outcomes has emerged from bothin vivo andin vitro investigations. This study aimed to elucidate the multifaceted nuances and gain a clearer comprehension of the role of ***: PubMed database was searched spanning from its inception to January 2022. The search criteria took the form of ( "Alzheimer’s disease" OR "AD" ) AND ( "transgenic mice model" OR "transgenic mouse model" ) AND ( "Triggering receptor expressed on myeloid cells" OR "TREM2" ). Inclusion criteria consisted of the following: (1) publication of original studies in English; (2) utilization of transgenic mouse models for AD research; and (3) reports addressing the subject of ***: A total of 43 eligible articles were identified. Our analysis addresses four pivotal queries concerning the interrelation of TREM2 with microglial function, Aβ accumulation, tau pathology, and inflammatory processes. However, the diverse inquiries posed yielded inconsistent responses. Nevertheless, the inconsistent roles of TREM2 within these AD mouse models potentially hinge upon factors such as age, sex, brain region, model type, and detection ***: This review substantiates the evolving understanding of TREM2’s disease progression-dependent impacts. Furthermore, it reviews the interplay between TREM2 and its effects across diverse tissues and temporal stages.

关键词： TREM2 Alzheimer’s disease Mouse model Microglia Amyloid-β accumulation Tau pathology Inflammation

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Mitochondrial recruitment in myelin:an anchor for myelin dynamics and plasticity?

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Neural Regeneration Research 2024年第7期19卷 1401-1402页

作者： Jean-David M.Gothié Timothy E.Kennedy department of Neurology and Neurosurgery Montreal Neurological InstituteMcGill UniversityMontrealQCCanada

Optimal propagation of neuronal electrical impulses depends on the insulation of axons by myelin,produced in the central nervous system by *** is an extension of the oligodendrocyte plasma membrane,which wraps around an axon to form a compact multi-layered *** is composed of a substantially higher proportion of lipids compared to other biological membranes and enriched in a small number of specialized proteins.

关键词： plasticity insulation dynamics

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Molecular mechanisms underlying microglial sensing and phagocytosis in synaptic pruning

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Neural Regeneration Research 2024年第6期19卷 1284-1290页

作者： Anran Huo Jiali Wang Qi Li Mengqi Li Yuwan Qi Qiao Yin Weifeng Luo Jijun Shi Qifei Cong Clinical Research Center of neurological Disease The Second Affiliated Hospital of Soochow UniversityInstitute of Neuroscience and Jiangsu Key Laboratory of Neuropsychiatric Diseases Soochow University department of Neurology and Clinical Research Center of neurological Disease The Second Affiliated Hospital of Soochow University

Microglia are the main non-neuronal cells in the central nervous system that have important roles in brain development and functional connectivity of neural circuits. In brain physiology, highly dynamic microglial processes are facilitated to sense the surrounding environment and stimuli. Once the brain switches its functional states, microglia are recruited to specific sites to exert their immune functions, including the release of cytokines and phagocytosis of cellular debris. The crosstalk of microglia between neurons, neural stem cells, endothelial cells, oligodendrocytes, and astrocytes contributes to their functions in synapse pruning, neurogenesis, vascularization, myelination, and blood-brain barrier permeability. In this review, we highlight the neuron-derived “find-me,” “eat-me,” and “don’t eat-me” molecular signals that drive microglia in response to changes in neuronal activity for synapse refinement during brain development. This review reveals the molecular mechanism of neuron-microglia interaction in synaptic pruning and presents novel ideas for the synaptic pruning of microglia in disease, thereby providing important clues for discovery of target drugs and development of nervous system disease treatment methods targeting synaptic dysfunction.

关键词： complement immune signals microglia molecular signal synapse elimination synapse formation synapse refinement synaptic pruning

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Enhancing the understanding between exercise and brain health:A new tool of oxygen imaging

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Journal of Sport and Health Science 2024年第6期13卷 751-752页

作者： Zhibo Wang Jianping Jia Innovation Center for neurological Disorders and department of Neurology Xuanwu HospitalCapital Medical UniversityBeijing 100053China

Oxygen is pivotal for brain metabolism,1 and understanding its dynamics within the cerebral cortex is essential for both fundamental neuroscience and clinical ***,Beinlich et al.2 introduced a novel tool,the Green enhanced Nano-lantern(GeNL),a bioluminescent oxygen sensor that allows for the real-time,high-resolution monitoring of oxygen distribution in the living mouse cerebral cortex.

关键词： metabolism cerebral

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Significant improvement after sensory tricks and trunk strength training for Parkinson’s disease with antecollis and camptocormia:A case report

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World Journal of Clinical Cases 2024年第2期12卷 443-450页

作者： Jia-Ren Wang Yue Hu department of Neurology and neurological Rehabilitation Shanghai Yangzhi Rehabilitation Hospital(Shanghai Sunshine Rehabilitation Center)Shanghai 201619China

BACKGROUND Patients with Parkinson's disease(PD)exhibit symptoms such as antecollis(AC)and camptocormia(CC).The pathology of these two conditions is ***,standard treatment methods have not been *** article reports the case of a 65-year-old female patient with AC and CC who was treated with central and peripheral interventions to alleviate *** SUMMARY We present the case of a 65-year-old female PD patient with AC and *** course of the disease was 5 *** was treated with rehabilitation strategies such as sensory tricks and trunk strength *** the inpatient period,we compared and analyzed the patient's gait,rehabilitation assessment scale score,and angles of her abnormal trunk posture in the first week,the third week,and the fifth *** patient's stride length increased,indicating that the patient's walking ability was *** Unified Parkinson's Disease Scale Part Three score and CC severity score ***,the score of the other scale *** addition,the patient showed significant improvements in AC,upper CC,and lower CC *** This case study suggested that sensory tricks and trunk strength training are beneficial and safe for patients with AC and CC.

关键词： Antecollis Camptocormia Parkinson's disease Sensory tricks Trunk strength training Case report

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Transcranial direct current stimulation efficacy in trigeminal neuralgia

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World Journal of Clinical Cases 2024年第5期12卷 1036-1038页

作者： Theodoros Fasilis Stylianos Gatzonis Panayiotis Patrikelis Stefanos Korfias Athanasia Alexoudi 1^(st) department of Neurosurgery National and Kapodistrian University of AthensAthens 10676Greece department of Neurology Neurological Institute of AthensAthens 10676Greece

Trigeminal neuralgia is a severe,disabling pain and its deafferentation remains a challenge for health *** direct current stimulation is a non-invasive stimulation technique which finds new utility in managing ***-fore,the introduction of alternative,non-invasive,safe,and effective methods should be considered in treating patients with trigeminal neuralgia unresponsive to conventional treatment.

关键词： Trigeminal neuralgia Patient-controlled intravenous analgesia Neuromodulation Transcranial direct current stimulation

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In patients who had a stroke or TIA, enlarged perivascular spaces in basal ganglia may cause future haemorrhagic strokes

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Stroke & Vascular Neurology 2024年第1期9卷 8-17,I0001-I0033页

作者： Yu Tian Mengxing Wang Yuesong Pan Xia Meng Xingquan Zhao Liping Liu Yongjun Wang Yilong Wang department of Neurology Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Chinese Institute for Brain Research BeijingChina National Center for neurological Diseases BeijingChina Advanced Innovation Center for Human Brain Protection Capital Medical UniversityBeijingChina China National Clinical Research Center for neurological Diseases BeijingChina

Introduction It remains unclear whether enlarged perivascular spaces(EPVS)predict poor clinical outcomes in patients with acute ischaemic stroke(AIS)or transient ischaemic attack(TIA).Method Data were obtained from the Third China National Stroke Registry *** estimated EPVS in basal ganglia(BG)and centrum semiovale(CSO)using a semiquantified scale(Grade from 0 to 4).Using Cox and logistic regression analyses,the associations of EPVS with 3-month and 1-year adverse outcomes(including recurrent stroke,ischaemic stroke,haemorrhagic stroke,combined vascular event,disability and mortality)were *** analyses of any association of cerebral small vessel disease at baseline and development of a small arterial occlusion(SAO)were *** Among 12603 patients with AIS/TIA,median age was 61.7±11.6 years,and 68.2%were *** adjusting for all potential confounders,frequent-to-severe BG-EPVS was associated with a decreased risk of recurrent ischaemic stroke(HR 0.71,95%CI 0.55 to 0.92,p=0.01)but an increased risk of haemorrhagic stroke(HR 1.99,95%CI 1.11 to 3.58,p=0.02)at 1 year after AIS/TIA,compared with none-to-mild *** with frequent-to-severe CSO-EPVS had a decreased risk of disability(OR 0.76,95%CI 0.62 to 0.92,p=0.004)and all-cause death(HR 0.55,95%CI 0.31 to 0.98,p=0.04)within 3-month but not 1-year follow-ups,compared with those with none-to-mild *** analyses showed that both BG-EPVS(HR 0.43,95%CI 0.21 to 0.87,p=0.02)and CSO-EPVS(HR 0.58,95%CI 0.35 to 0.95,p=0.03)were associated with a decreased risk of subsequent ischaemic stroke in patients with SAO during 1-year *** BG-EPVS increased the risk of haemorrhagic stroke in patients already with AIS/TIA within 1 ***,caution is recommended when selecting antithrombotic agents for secondary stroke prevention in patients with AIS/TIA and more severe BG-EPVS.

关键词： patients haemorrhagic prevention

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Spi1 regulates the microglial/macrophage inflammatory response via the PI3K/AKT/mTOR signaling pathway after intracerebral hemorrhage

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Neural Regeneration Research 2024年第1期19卷 161-170页

作者： Guoqiang Zhang Jianan Lu Jingwei Zheng Shuhao Mei Huaming Li Xiaotao Zhang An Ping Shiqi Gao Yuanjian Fang Jun Yu department of Neurosurgery The Second Affiliated Hospital of Zhejiang University School of MedicineHangzhouZhejiang ProvinceChina department of Neurosurgery Huashan Hospital of Fudan University School of MedicineShanghaiChina Clinical Research Center for neurological Diseases of Zhejiang Province HangzhouZhejiang ProvinceChina Key Laboratory of Precise Treatment and Clinical Translational Research of neurological Diseases HangzhouZhejiang ProvinceChina

Preclinical and clinical studies have shown that microglia and macrophages participate in a multiphasic brain damage repair process following intracerebral *** E26 transformation-specific sequence-related transcription factor Spi1 regulates microglial/macrophage commitment and ***,the effect of Spi1 on intracerebral hemorrhage remains *** this study,we found that Spi1 may regulate recovery from the neuroinflammation and neurofunctional damage caused by intracerebral hemorrhage by modulating the microglial/macrophage *** showed that high Spi1expression in microglia/macrophages after intracerebral hemorrhage is associated with the activation of many pathways that promote phagocytosis,glycolysis,and autophagy,as well as debris clearance and sustained ***,microglia with higher levels of Soil expression were chara cterized by activation of pathways associated with a variety of hemorrhage-related cellular processes,such as complement activation,angiogenesis,and *** conclusion,our results suggest that Spi1 plays a vital role in the microglial/macrophage inflammatory response following intracerebral *** new insight into the regulation of Spi1 and its target genes may advance our understanding of neuroinflammation in intracerebral hemorrhage and provide therapeutic targets for patients with intracerebral hemorrhage.

关键词： intracerebral hemorrhage macrophage microglia neuroinflammation phagocytosis PI3K/AKT/mTOR signaling pathway Spi1 transcriptomics

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Connecting cellular mechanisms and extracellular vesicle cargo in traumatic brain injury

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Neural Regeneration Research 2024年第10期19卷 2119-2131页

作者： Nikita Ollen-Bittle Austyn D.Roseborough Wenxuan Wang Jeng-liang D.Wu Shawn N.Whitehead department of Anatomy and Cell Biology Western UniversityLondonONCanada Schulich School of Medicine and Dentistry Western UniversityLondonONCanada Deparment of Clinical neurological Sciences Western UniversityLondonONCanada

Traumatic brain injury is followed by a cascade of dynamic and complex events occurring at the cellular level. These events include: diffuse axonal injury, neuronal cell death, blood-brain barrier break down, glial activation and neuroinflammation, edema, ischemia, vascular injury, energy failure, and peripheral immune cell infiltration. The timing of these events post injury has been linked to injury severity and functional outcome. Extracellular vesicles are membrane bound secretory vesicles that contain markers and cargo pertaining to their cell of origin and can cross the blood-brain barrier. These qualities make extracellular vesicles intriguing candidates for a liquid biopsy into the pathophysiologic changes occurring at the cellular level post traumatic brain injury. Herein, we review the most commonly reported cargo changes in extracellular vesicles from clinical traumatic brain injury samples. We then use knowledge from animal and in vitro models to help infer what these changes may indicate regrading cellular responses post traumatic brain injury. Future research should prioritize labeling extracellular vesicles with markers for distinct cell types across a range of timepoints post traumatic brain injury.

关键词： axonal injury biomarkers blood-brain barrier chronic traumatic encephalopathy extracellular vesicles glial activation neuroinflammation traumatic brain injury

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Association of DNA methylation/demethylation with the functional outcome of stroke in a hyperinflammatory state

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Neural Regeneration Research 2024年第10期19卷 2229-2239页

作者： Yubo Wang Ling Zhang Tianjie Lyu Lu Cui Shunying Zhao Xuechun Wang Meng Wang Yongjun Wang Zixiao Li Vascular Neurology Department of NeurologyBeijing Tiantan HospitalCapital Medical UniversityBeijingChina China National Clinical Research Center for neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina National Center for Healthcare Quality Management in neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Chinese Institute for Brain Research BeijingChina Research Unit of Artificial Intelligence in Cerebrovascular Disease Chinese Academy of Medical SciencesBeijingChina Beijing Engineering Research Center of Digital Healthcare for neurological Diseases BeijingChina

Inflammation is closely related to stroke prognosis, and high inflammation status leads to poor functional outcome in stroke. DNA methylation is involved in the pathogenesis and prognosis of stroke. However, the effect of DNA methylation on stroke at high levels of inflammation is unclear. In this study, we constructed a hyperinflammatory cerebral ischemia mouse model and investigated the effect of hypomethylation and hypermethylation on the functional outcome. We constructed a mouse model of transient middle cerebral artery occlusion and treated the mice with lipopolysaccharide to induce a hyperinflammatory state. To investigate the effect of DNA methylation on stroke, we used small molecule inhibitors to restrain the function of key DNA methylation and demethylation enzymes. 2,3,5-Triphenyltetrazolium chloride staining, neurological function scores, neurobehavioral tests, enzyme-linked immunosorbent assay, quantitative reverse transcription PCR and western blot assay were used to evaluate the effects after stroke in mice. We assessed changes in the global methylation status by measuring DNA 5-mc and DNA 5-hmc levels in peripheral blood after the use of the inhibitor. In the group treated with the DNA methylation inhibitor, brain tissue 2,3,5-triphenyltetrazolium chloride staining showed an increase in infarct volume, which was accompanied by a decrease in neurological scores and worsening of neurobehavioral performance. The levels of inflammatory factors interleukin 6 and interleukin-1 beta in ischemic brain tissue and plasma were elevated, indicating increased inflammation. Related inflammatory pathway exploration showed significant overactivation of nuclear factor kappa B. These results suggested that inhibiting DNA methylation led to poor functional outcome in mice with high inflammation following stroke. Further, the effects were reversed by inhibition of DNA demethylation. Our findings suggest that DNA methylation regulates the inflammatory response in stroke

关键词： DNA demethylation DNA methylation DNMT3A functional outcome hyperinflammatory state interleukin neuroinflammation stroke TET2

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