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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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The bumpy road of purinergic inhibitors to clinical application in immune-mediated diseases

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Neural Regeneration Research 2024年第6期19卷 1206-1211页

作者： Matihias T.Wyss Christine Heuer Marina Herwerth Institute of Pharmacology and Toxicology University of Zurich Neuroscience Center Zurich (ZNZ) University of Zurich and ETH Zurich 3. Neurology Department University Hospital of Zurich

Purinergic signaling plays important roles throughout the body in the regulation of organ functions during and following the disruption of homeostasis. This is also reflected by the widespread expression of two families of purinergic receptors(P1 and P2) with numerous subtypes. In the last few decades, there has been increasing evidence that purinergic signaling plays an important role in the regulation of immune functions. Mainly, signals mediated by P2 receptors have been shown to contribute to immune system-mediated pathologies. Thus, interference with P2 receptors may be a promising strategy for the modulation of immune responses. Although only a few clinical studies have been conducted in isolated entities with limited success, preclinical work suggests that the use of P2 receptor inhibitors may bear some promise in various autoimmune diseases. Despite the association of P2 receptors with several disorders from this field, the use of P2 receptor antagonists in clinical therapy is still very scarce. In this narrative review, we briefly review the involvement of the purinergic system in immunological responses and clinical studies on the effect of purinergic inhibition on autoimmune processes. We then open the aperture a bit and show some preclinical studies demonstrating a potential effect of purinergic blockade on autoimmune events. Using suramin, a non-specific purinergic inhibitor, as an example, we further show that off-target effects could be responsible for observed effects in immunological settings, which may have interesting implications. Overall, we believe that it is worthwhile to further investigate this hitherto underexplored area.

关键词： autoimmune diseases neurological disorders purinergic system P2 receptor inhibitors suramin

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Skeletal muscle as a molecular and cellular biomarker of disease progression in amyotrophic lateral sclerosis:a narrative review

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Neural Regeneration Research 2024年第4期19卷 747-753页

作者： Peter H.King department of neurology and Center for Neurodegeneration and Experimental Therapeutics The University of Alabama at BirminghamBirminghamALUSA Birmingham Veterans Affairs Medical Center BirminghamALUSA

Amyotrophic lateral sclerosis is a fatal multisystemic neurodegenerative disease with motor neurons being a primary *** progressive weakness is a hallmark feature of amyotrophic lateral sclerosis,there is considerable heterogeneity,including clinical presentation,progression,and the underlying triggers for disease *** on longitudinal studies with families harboring amyotrophic lateral sclerosis-associated gene mutations,it has become apparent that overt disease is preceded by a prodromal phase,possibly in years,where compensatory mechanisms delay symptom *** 85-90%of amyotrophic lateral sclerosis is sporadic,there is a strong need for identifying biomarkers that can detect this prodromal phase as motor neurons have limited capacity for *** Food and Drug Administration-approved therapies work by slowing the degenerative process and are most effective early in the *** muscle,including the neuromuscular junction,manifests abnormalities at the earliest stages of the disease,before motor neuron loss,making it a promising source for identifying biomarkers of the prodromal *** accessibility of muscle through biopsy provides a lens into the distal motor system at earlier stages and in real *** advent of“omics”technology has led to the identification of numerous dysregulated molecules in amyotrophic lateral sclerosis muscle,ranging from coding and non-coding RNAs to proteins and *** technology has opened the door for identifying biomarkers of disease activity and providing insight into disease mechanisms.A major challenge is correlating the myriad of dysregulated molecules with clinical or histological progression and understanding their relevance to presymptomatic phases of *** are two major goals of this *** first is to summarize some of the biomarkers identified in human amyotrophic lateral sclerosis muscle that have a clinicopathological correlation with disease activi

关键词： amyotrophic lateral sclerosis biomarkers clinicopathological correlation disease progression muscle biomarkers neurogenic atrophy neuromuscular junction non-coding RNAs presymptomatic stages skeletal muscle SOD1G93A mouse model

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Heterogeneity of mature oligodendrocytes in the central nervous system

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Neural Regeneration Research 2025年第5期20卷 1336-1349页

作者： Chao Weng Adam M.R.Groh Moein Yaqubi Qiao-Ling Cui Jo Anne Stratton G.R.Wayne Moore Jack P.Antel Neuroimmunology Unit Montreal Neurological Institute-HospitalDepartment of Neurology and NeurosurgeryMcGill UniversityMontrealQCCanada department of neurology Renmin Hospital of Wuhan UniversityWuhanHubei ProvinceChina

Mature oligodendrocytes form myelin sheaths that are crucial for the insulation of axons and efficient signal transmission in the central nervous *** evidence has challenged the classical view of the functionally static mature oligodendrocyte and revealed a gamut of dynamic functions such as the ability to modulate neuronal circuitry and provide metabolic support to *** the recognition of potential heterogeneity in mature oligodendrocyte function,a comprehensive summary of mature oligodendrocyte diversity is *** delve into early 20th-century studies by Robertson and Río-Hortega that laid the foundation for the modern identification of regional and morphological heterogeneity in mature ***,recent morphologic and functional studies call into question the long-assumed homogeneity of mature oligodendrocyte function through the identification of distinct subtypes with varying myelination ***,modern molecular investigations,employing techniques such as single cell/nucleus RNA sequencing,consistently unveil at least six mature oligodendrocyte subpopulations in the human central nervous system that are highly transcriptomically diverse and vary with central nervous system *** and disease related mature oligodendrocyte variation denotes the impact of pathological conditions such as multiple sclerosis,Alzheimer's disease,and psychiatric ***,caution is warranted when subclassifying mature oligodendrocytes because of the simplification needed to make conclusions about cell identity from temporally confined *** studies leveraging advanced techniques like spatial transcriptomics and single-cell proteomics promise a more nuanced understanding of mature oligodendrocyte *** research avenues that precisely evaluate mature oligodendrocyte heterogeneity with care to understand the mitigating influence of species,sex,central nervous system region,age,and disease,

关键词： aging central nervous system diseases electron microscopy heterogeneity immunohistochemistry myelin sheath natural history neuroglia oligodendroglia single-cell gene expression analysis

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Post-acute ischemic stroke hyperglycemia aggravates destruction of the blood-brain barrier

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Neural Regeneration Research 2024年第6期19卷 1344-1350页

作者： Tianqi Xu Jianhong Yang Yao Xu Xiaofeng Wang Xiang Gao Jie Sun Chenhui Zhou Yi Huang department of neurology The First Affiliated Hospital of Ningbo University department of General Surgery The First Affiliated Hospital of Ningbo University department of Neurosurgery The First Affiliated Hospital of Ningbo University Key Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang Province

Post-acute ischemic stroke hyperglycemia increases the risk of hemorrhagic transformation, which is associated with blood-brain barrier disruption. Brain microvascular endothelial cells are a major component of the blood-brain barrier. Intercellular mitochondrial transfer has emerged as a novel paradigm for repairing cells with mitochondrial dysfunction. In this study, we first investigated whether mitochondrial transfer exists between brain microvascular endothelial cells, and then investigated the effects of post-acute ischemic stroke hyperglycemia on mitochondrial transfer between brain microvascular endothelial cells. We found that healthy brain microvascular endothelial cells can transfer intact mitochondria to oxygen glucose deprivation-injured brain microvascular endothelial cells. However, post-oxygen glucose deprivation hyperglycemia hindered mitochondrial transfer and exacerbated mitochondrial dysfunction. We established an in vitro brain microvascular endothelial cell model of the blood-brain barrier. We found that post-acute ischemic stroke hyperglycemia reduced the overall energy metabolism levels of brain microvascular endothelial cells and increased permeability of the blood-brain barrier. In a clinical study, we retrospectively analyzed the relationship between post-acute ischemic stroke hyperglycemia and the severity of hemorrhagic transformation. We found that post-acute ischemic stroke hyperglycemia serves as an independent predictor of severe hemorrhagic transformation. These findings suggest that post-acute ischemic stroke hyperglycemia can aggravate disruption of the blood-brain barrier by inhibiting mitochondrial transfer.

关键词： acute ischemic stroke blood-brain barrier brain microvascular endothelial cells mitochondrial transfer stress hyperglycemia

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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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Use of donepezil for neurocognitive recovery after brain injury in adult and pediatric populations:a scoping review

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Neural Regeneration Research 2024年第8期19卷 1686-1695页

作者： Avery L.Miller Nathan K.Evanson J.Michael Taylor University of Cincinnati College of Medicine CincinnatiOHUSA department of Pediatrics University of CincinnatiCincinnatiOHUSA department of neurology and Rehabilitation Medicine University of CincinnatiCincinnatiOHUSA Division of Pediatric Rehabilitation Medicine Cincinnati Children’s Hospital Medical CenterCincinnatiOHUSA Division of neurology Cincinnati Children’s Hospital Medical CenterCincinnatiOHUSA

There are few pharmacologic options for the treatment of cognitive deficits associated with traumatic brain injury in pediatric *** inhibitors such as donepezil have been evaluated in adult patients after traumatic brain injury,but relatively less is known about the effect in pediatric *** goal of this review is to identify knowledge gaps in the efficacy and safety of acetylcholinesterase inhibito rs as a potential a djuvant treatment fo r neurocognitive decline in pediatric patients with traumatic brain *** queried PubMed to identify literature published from database inception thro ugh June 2023 desc ribing the use of donepezil in young adult traumatic brain injury and pediatric patients with predefined *** on preselected search criteria,340 unique papers we re selected for title and abstra ct ***-two reco rds were reviewed in full after eliminating preclinical studies and pape rs outside the scope of the *** adult traumatic brain injury,we review results from 14 papers detailing 227 subjects where evidence suggests donepezil is well tole rated and shows both objective and patient-reported efficacy for reducing cognitive *** children,3 pape rs report on 5 children recovering from traumatic brain injury,showing limited *** additional 15 pediatric studies conducted in populations at risk for cognitive dysfunction provide a broader look at safety and efficacy in 210 patients in the pediatric age *** its promise for efficacy in adults with traumatic brain injury and tole rability in pediatric patients,we believe further study of donepezil for children and adolescents with traumatic brain injury is warranted.

关键词： acetylcholinesterase inhibitor adult cognition donepezil pediatrics traumatic brain injury

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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 al.

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Exosomes:the next-generation therapeutic platform for ischemic stroke

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Neural Regeneration Research 2025年第5期20卷 1221-1235页

作者： Wenjing Yin Hongyin Ma Yang Qu Jiaxin Ren Yingying Sun Zhen-Ni Guo Yi Yang Stroke Center Department of NeurologyFirst Hospital of Jilin UniversityChangchunJilin ProvinceChina Neuroscience Research Center Department of NeurologyFirst Hospital of Jilin UniversityChangchunJilin ProvinceChina

Current therapeutic strategies for ischemic stroke fall short of the desired objective of neurological functional ***,there is an urgent need to develop new methods for the treatment of this *** are natural cell-derived vesicles that mediate signal transduction between cells under physiological and pathological *** have low immunogenicity,good stability,high delivery efficiency,and the ability to cross the blood–brain *** physiological properties of exosomes have the potential to lead to new breakthroughs in the treatment of ischemic *** rapid development of nanotechnology has advanced the application of engineered exosomes,which can effectively improve targeting ability,enhance therapeutic efficacy,and minimize the dosages *** in technology have also driven clinical translational research on *** this review,we describe the therapeutic effects of exosomes and their positive roles in current treatment strategies for ischemic stroke,including their antiinflammation,anti-apoptosis,autophagy-regulation,angiogenesis,neurogenesis,and glial scar formation reduction ***,it is worth noting that,despite their significant therapeutic potential,there remains a dearth of standardized characterization methods and efficient isolation techniques capable of producing highly purified *** optimization strategies should prioritize the exploration of suitable isolation techniques and the establishment of unified workflows to effectively harness exosomes for diagnostic or therapeutic applications in ischemic ***,our review aims to summarize our understanding of exosome-based treatment prospects in ischemic stroke and foster innovative ideas for the development of exosome-based therapies.

关键词： blood–brain barrier electroacupuncture engineering exercise exosomes ischemic stroke mesenchymal stem cells microglia neuroprotection stents

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Predictive value of neutrophil-to-lymphocyte ratio in coronary chronic total occlusion patients

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Journal of Geriatric Cardiology 2024年第5期21卷 542-549页

作者： Qian LI Yue YU Ya-Qiong ZHOU Yi ZHAO Jin WU Yuan-Jing WU Bin DU Pei-Jian WANG Tao ZHENG department of Cardiovascular Medicine the First Affiliated Hospital of Xi’an Jiaotong UniversityXi’anChina department of Cardiology First Affiliated Hospital of Chengdu Medical CollegeChengduChina department of neurology the First Affiliated Hospital of Xi’an Jiaotong UniversityXi’anChina

BACKGROUND The neutrophil to lymphocyte ratio(NLR)has been reported as a novel predictor for atherosclerosis and car-diovascular *** study aimed to determine the effects of NLR on long-term clinical outcomes of chronic total occlusion(CTO)*** A total of 670 patients with CTO who met the inclusion criteria were included at the end of the follow-up *** were divided into tertiles according to their baseline NLR levels at admission:low(n=223),intermediate(n=223),and high(n=224).The incidence of major adverse cardiac events(MACEs)during the follow-up period,including all-cause death,nonfatal myocardial infarction(MI),or ischemia-driven revascularization,were compared among the three *** Major adverse cardiac events were observed in 27 patients(12.1%)in the low tertile,40(17.9%)in the intermediate tertile,and 61(27.2%)in the high NLR tertile(P<0.001).Kaplan-Meier analysis demonstrated a significantly higher incidence of MACE,ischemia-driven coronary revascularization,non-fatal MI,and mortality in patients within the high tertile than those in the low and intermediate groups(all P<0.001).Multivariable COX regression analysis showed that the high tertile of baseline NLR level showed a strong association with the risk of MACE(hazard ratio[HR]=2.21;95%confidence interval[CI]:1.21-4.03;P=0.009),ischemia-driven coronary revascularization(HR=3.19;95%CI:1.56-6.52;P=0.001),MI(HR=2.61;95%CI:1.35-5.03;P=0.043)and mortality(HR=3.78;95%CI:1.65-8.77;P=0.001).CONCLUSION Our findings suggest that NLR is an inexpensive and readily available biomarker that can independently pre-dict cardiovascular risk in patients with CTO.

关键词： patients coronary occlusion

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