Hasil untuk "Neurology. Diseases of the nervous system"

Alexei Verkhratsky, A. Butt, Baoman Li et al.

Astroglia are a broad class of neural parenchymal cells primarily dedicated to homoeostasis and defence of the central nervous system (CNS). Astroglia contribute to the pathophysiology of all neurological and neuropsychiatric disorders in ways that can be either beneficial or detrimental to disorder outcome. Pathophysiological changes in astroglia can be primary or secondary and can result in gain or loss of functions. Astroglia respond to external, non-cell autonomous signals associated with any form of CNS pathology by undergoing complex and variable changes in their structure, molecular expression, and function. In addition, internally driven, cell autonomous changes of astroglial innate properties can lead to CNS pathologies. Astroglial pathophysiology is complex, with different pathophysiological cell states and cell phenotypes that are context-specific and vary with disorder, disorder-stage, comorbidities, age, and sex. Here, we classify astroglial pathophysiology into (i) reactive astrogliosis, (ii) astroglial atrophy with loss of function, (iii) astroglial degeneration and death, and (iv) astrocytopathies characterised by aberrant forms that drive disease. We review astroglial pathophysiology across the spectrum of human CNS diseases and disorders, including neurotrauma, stroke, neuroinfection, autoimmune attack and epilepsy, as well as neurodevelopmental, neurodegenerative, metabolic and neuropsychiatric disorders. Characterising cellular and molecular mechanisms of astroglial pathophysiology represents a new frontier to identify novel therapeutic strategies.

J. Dalmau, C. Geis, F. Graus

Wenjing Xu, Yi Huang, Rongbin Zhou

Neuroinflammation plays an important role in the pathogenesis of various central nervous system (CNS) diseases. The NLRP3 inflammasome is an important intracellular multiprotein complex composed of the innate immune receptor NLRP3, the adaptor protein ASC, and the protease caspase-1. The activation of the NLRP3 inflammasome can induce pyroptosis and the release of the proinflammatory cytokines IL-1β and IL-18, thus playing a central role in immune and inflammatory responses. Recent studies have revealed that the NLRP3 inflammasome is activated in the brain to induce neuroinflammation, leading to further neuronal damage and functional impairment, and contributes to the pathological process of various neurological diseases, such as multiple sclerosis, Parkinson’s disease, Alzheimer’s disease, and stroke. In this review, we summarize the important role of the NLRP3 inflammasome in the pathogenesis of neuroinflammation and the pathological course of CNS diseases and discuss potential approaches to target the NLRP3 inflammasome for the treatment of CNS diseases.

Sezen Vatansever, A. Schlessinger, Daniel Wacker et al.

Neurological disorders significantly outnumber diseases in other therapeutic areas. However, developing drugs for central nervous system (CNS) disorders remains the most challenging area in drug discovery, accompanied with the long timelines and high attrition rates. With the rapid growth of biomedical data enabled by advanced experimental technologies, artificial intelligence (AI) and machine learning (ML) have emerged as an indispensable tool to draw meaningful insights and improve decision making in drug discovery. Thanks to the advancements in AI and ML algorithms, now the AI/ML‐driven solutions have an unprecedented potential to accelerate the process of CNS drug discovery with better success rate. In this review, we comprehensively summarize AI/ML‐powered pharmaceutical discovery efforts and their implementations in the CNS area. After introducing the AI/ML models as well as the conceptualization and data preparation, we outline the applications of AI/ML technologies to several key procedures in drug discovery, including target identification, compound screening, hit/lead generation and optimization, drug response and synergy prediction, de novo drug design, and drug repurposing. We review the current state‐of‐the‐art of AI/ML‐guided CNS drug discovery, focusing on blood–brain barrier permeability prediction and implementation into therapeutic discovery for neurological diseases. Finally, we discuss the major challenges and limitations of current approaches and possible future directions that may provide resolutions to these difficulties.

Yan-Ying Fan, Jing Huo

Jéssica Silva dos Santos, João Pedro Gonçalves Cirino, Patrícia de Oliveira Carvalho et al.

Kaempferol (KPF) is a flavonoid antioxidant found in fruits and vegetables. Many studies have described the beneficial effects of dietary KPF in reducing the risk of chronic diseases, especially cancer. Nevertheless, little is known about the cellular and molecular mechanisms underlying KPF actions in the central nervous system (CNS). Also, the relationship between KPF structural properties and their glycosylation and the biological benefits of these compounds is unclear. The aim of this study was to review studies published in the PubMed database during the last 10 years (2010–2020), considering only experimental articles that addressed the isolated cell effect of KPF (C15H10O6) and its derivatives in neurological diseases such as Alzheimer's disease, Parkinson, ischemia stroke, epilepsy, major depressive disorder, anxiety disorders, neuropathic pain, and glioblastoma. 27 publications were included in the present review, which presented recent advances in the effects of KPF on the nervous system. KPF has presented a multipotential neuroprotective action through the modulation of several proinflammatory signaling pathways such as the nuclear factor kappa B (NF-kB), p38 mitogen-activated protein kinases (p38MAPK), serine/threonine kinase (AKT), and β-catenin cascade. In addition, there are different biological benefits and pharmacokinetic behaviors between KPF aglycone and its glycosides. The antioxidant nature of KPF was observed in all neurological diseases through MMP2, MMP3, and MMP9 metalloproteinase inhibition; reactive oxygen species generation inhibition; endogenous antioxidants modulation as superoxide dismutase and glutathione; formation and aggregation of beta-amyloid (β-A) protein inhibition; and brain protective action through the modulation of brain-derived neurotrophic factor (BDNF), important for neural plasticity. In conclusion, we suggest that KPF and some glycosylated derivatives (KPF-3-O-rhamnoside, KPF-3-O-glucoside, KPF-7-O-rutinoside, and KPF-4′-methyl ether) have a multipotential neuroprotective action in CNS diseases, and further studies may make the KPF effect mechanisms in those pathologies clearer. Future in vivo studies are needed to clarify the mechanism of KPF action in CNS diseases as well as the impact of glycosylation on KPF bioactivity.

Zhang Hui, Lai-Fa Wang, Xue-qin Wang et al.

Abstract The flavonoid compound chinonin is one of the main active components of Rhizoma anemarrhena with multiple activities, including anti-inflammatory and antioxidant properties, protection of mitochondrial function and regulation of immunity. In this paper, we reviewed recent research progress on the protective effect of chinonin on brain injury in neurological diseases. “Chinonin” OR “Mangiferin” AND “Nervous system diseases” OR “Neuroprotection” was used as the terms for search in PumMed. After discarding duplicated and irrelevant articles, a total of 23 articles relevant to chinonin published between 2012 and 2023 were identified in our study.

Makoto Kawahito, Keitaro Murayama, Hirofumi Tomiyama et al.

IntroductionSensory phenomena (SP) are subjective experiences, such as feelings of discomfort or incompleteness, which often precede repetitive behaviors in patients with obsessive-compulsive disorder (OCD). Although previous studies have shown that SP are common in early-onset OCD, the relationship between age at onset and SP severity remains unclear.MethodsThis cross-sectional study included 30 drug-naive patients with OCD, without comorbid psychiatric or medical/neurological disorders, and with at least one lifetime SP. SP severity was assessed using the University of São Paulo Sensory Phenomena Scale (USPSPS). Multiple regression analysis was conducted to examine the association between age at onset and SP severity, controlling for sex, autistic traits, and obsessive-compulsive symptom severity. Sensitivity analyses evaluated illness duration and anxiety and used a two-part analysis to address the floor at USPSPS = 0. Robustness was assessed using bias-corrected (BC) bootstrap 95% confidence intervals and influence diagnostics.ResultsEarlier age at onset was associated with greater SP severity (B = −0.171, p = 0.007; BC bootstrap 95% CI −0.300 to −0.064). Sensitivity analyses, including models additionally adjusting for illness duration or anxiety, and influence diagnostics, supported the robustness of this association. In a two-part analysis, autistic traits were associated with the presence of current SP, whereas earlier onset was associated with greater SP severity.DiscussionEarlier onset of OCD was associated with more severe SP after adjustment for clinical covariates. These findings may be consistent with a neurodevelopmental contribution to SP severity in OCD. Further longitudinal and qualitative studies on SP are warranted.

Hai-Li Pan, Jia-Yi Ge, Zi-Ang Zhang et al.

Myeloid differentiation primary response 88 (MyD88), a central adaptor protein governing Toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) signaling cascades, is increasingly recognized as a pivotal mediator of neuroimmune interactions and neuromodulation. Beyond its canonical immune functions, emerging evidence reveals widespread MyD88 expression throughout the nervous system, where it plays functional roles in both glial populations and neuronal networks. While previous reviews have largely focused on glial mechanisms, recent studies highlight a complex, often overlooked aspect: the dual role of neuronal MyD88 signaling in orchestrating neurodevelopment while paradoxically driving neuroinflammation and synaptic dysregulation. Given the growing interest in innate immunity's involvement in central nervous system (CNS) diseases, a timely synthesis of MyD88 biology-from molecular mechanisms to therapeutic implications-is essential to bridge the fields of immunology and neuroscience. This article provides a comprehensive review of MyD88, synthesizing contemporary insights into its multifaceted regulatory roles in neural homeostasis and pathogenesis. We place particular emphasis on its mechanistic contributions to brain injury, chronic pain, and neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). Furthermore, we evaluate innovative therapeutic approaches targeting MyD88-dependent pathways, highlighting recent pharmacotherapeutic advances and their neuroprotective potential. Finally, addressing the limitations of current strategies, we advocate for a new framework focused on developing therapeutics with increased cell selectivity, thereby advancing the precision and translational potential of MyD88-targeted interventions.

A. F. Salvador, Nora Abduljawad, Jonathan Kipnis

Since its recent discovery, the meningeal lymphatic system has reshaped our understanding of central nervous system (CNS) fluid exchange, waste clearance, immune cell trafficking, and immune privilege. Meningeal lymphatics have also been demonstrated to functionally modify the outcome of neurological disorders and their responses to treatment, including brain tumors, inflammatory diseases such as multiple sclerosis, CNS injuries, and neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases. In this review, we discuss recent evidence of the contribution of meningeal lymphatics to neurological diseases, as well as the available experimental methods for manipulating meningeal lymphatics in these conditions. Finally, we also provide a discussion of the pressing questions and challenges in utilizing meningeal lymphatics as a prime target for CNS therapeutic intervention and possibly drug delivery for brain disorders.

Kira DiClemente-Bosco, Caroline Kuo, Goodman Sibeko et al.

Background In South Africa, rates of HIV and alcohol use are among the highest globally, with a detrimental synergistic relationship. Screening, Brief Intervention, and Referral to Treatment (SBIRT) is an evidence-based, cost-effective approach to identifying people at risk of alcohol-related problems to deliver early intervention. We developed and deployed a cascading train-the-trainer model to promote SBIRT implementation in a large nongovernmental organization offering HIV services across South Africa. Method Between 2021 and 2022, we completed preparatory activities including designing scalable training resources prior to rolling out the train-the-trainer model across two South African provinces. We conducted a comprehensive assessment of outcomes at the trainer- (knowledge, fidelity), provider- (attitudes, confidence, perceived implementation potential, adoption), and client-encounter (reach) levels over approximately one year. Results We trained 12 novice trainers who then trained 206 providers to implement SBIRT. Trainer SBIRT knowledge increased pre- to posttraining, and fidelity of training delivery was high (99.0% of elements covered across sessions). Provider attitudes, confidence, and perceived implementation potential increased over time, and 64% of providers adopted SBIRT. Reach of the model varied by component, with 41,793 clients screened by trained providers. Of those screening positive for risky alcohol use, 86% received brief intervention (BI) and 53% received referral to treatment (RT). Additionally, 15,353 clients who did not screen as having risky alcohol use received BI and 1,122 received RT. Conclusion Results indicated that the cascading training model was delivered with high fidelity, associated with improvements in all provider outcomes, and reached high numbers of clients for the screening component of the model. Rates of BI and RT delivery were moderate to high, though data suggested over-application of these elements with some clients, highlighting the tension between reach and fidelity. Lessons learned will inform future scale-out of this model in HIV service settings in low- and middle-income countries.

Manuela Daniela Danu, George Marica, Constantin Suciu et al.

The rapidly increasing volume of electronic health record (EHR) data underscores a pressing need to unlock biomedical knowledge from unstructured clinical texts to support advancements in data-driven clinical systems, including patient diagnosis, disease progression monitoring, treatment effects assessment, prediction of future clinical events, etc. While contextualized language models have demonstrated impressive performance improvements for named entity recognition (NER) systems in English corpora, there remains a scarcity of research focused on clinical texts in low-resource languages. To bridge this gap, our study aims to develop multiple deep contextual embedding models to enhance clinical NER in the cardiology domain, as part of the BioASQ MultiCardioNER shared task. We explore the effectiveness of different monolingual and multilingual BERT-based models, trained on general domain text, for extracting disease and medication mentions from clinical case reports written in English, Spanish, and Italian. We achieved an F1-score of 77.88% on Spanish Diseases Recognition (SDR), 92.09% on Spanish Medications Recognition (SMR), 91.74% on English Medications Recognition (EMR), and 88.9% on Italian Medications Recognition (IMR). These results outperform the mean and median F1 scores in the test leaderboard across all subtasks, with the mean/median values being: 69.61%/75.66% for SDR, 81.22%/90.18% for SMR, 89.2%/88.96% for EMR, and 82.8%/87.76% for IMR.

Li Zhou, Feilong Tan, Xue Zhang et al.

Ginsenosides are the primary component discernible from ginseng, including Rb1, Rb2, Rd, Rg1, Rg2, and compound K, and so forth. They have been shown to have multiple pharmacological activities. In recent years, more and more studies have been devoted to the neuroprotection of various ginsenosides against neurological diseases and their potential mechanisms. This paper comprehensively summarizes and reviews the neuroprotective effects of various ginsenosides on neurological diseases, especially acute and chronic neurodegenerative diseases, and their mechanisms, as well as their potential therapeutic applications to promote neuroprotection in disease prevention, treatment, and prognosis. Briefly, ginsenosides exert effective neuroprotective effects on neurological conditions, including stroke, Alzheimer's disease, Parkinson's disease, and brain/spinal cord injuries through a variety of molecular mechanisms, including anti‐inflammatory, antioxidant, and anti‐apoptotic. Among them, some signaling pathways play important roles in related processes, such as PI3K/Akt, TLR4/NF‐κB, ROS/TXNIP/NLRP3, HO‐1/Nrf2, Wnt/β‐catenin, and Ca2+ pathway. In conclusion, the present study reviews the research progress on the neuroprotective effects of ginsenosides in the last decade, with the aim of furnishing essential theoretical underpinning and effective references for further research and exploration of the multiple medicinal values of Chinese herbal medicines and their small molecule compounds, including ginseng and panax ginseng. Because there is less evidence in the existing clinical studies, future research should be focused on clinical trials in order to truly reflect the clinical value of various ginsenosides for the benefit of patients.

Weiwei Zou, Min Li, Xiaolei Wang et al.

Vincenzo Marcelli, Vincenzo Marcelli, Beatrice Giannoni et al.

Downbeat nystagmus (DBN) is a neuro-otological finding frequently encountered by clinicians dealing with patients with vertigo. Since DBN is a finding that should be understood because of central vestibular dysfunction, it is necessary to know how to frame it promptly to suggest the correct diagnostic-therapeutic pathway to the patient. As knowledge of its pathophysiology has progressed, the importance of this clinical sign has been increasingly understood. At the same time, clinical diagnostic knowledge has increased, and it has been recognized that this sign may occur sporadically or in association with others within defined clinical syndromes. Thus, in many cases, different therapeutic solutions have become possible. In our work, we have attempted to systematize current knowledge about the origin of this finding, the clinical presentation and current treatment options, to provide an overview that can be used at different levels, from the general practitioner to the specialist neurologist or neurotologist.

Blake Fernandino, Moein Samak Bisheh

Timely detection of illnesses is vital to prevent severe infections and ensure effective treatment, as it's always better to prevent diseases than to cure them. Sadly, many patients remain undiagnosed until their conditions worsen, resulting in high death rates. Expert systems offer a solution by automating early-stage diagnoses using a fuzzy rule-based approach. Our study gathered data from various sources, including hospitals, to develop an expert system aimed at identifying early signs of diseases, particularly heart conditions. The diagnostic process involves collecting and processing test results using the expert system, which categorizes disease risks and aids physicians in treatment decisions. By incorporating expert systems into clinical practice, we can improve the accuracy of disease detection and address challenges in patient management, particularly in areas with limited medical resources.

Tianqi Wei, Zhi Chen, Xin Yu

Plant disease recognition is a critical task that ensures crop health and mitigates the damage caused by diseases. A handy tool that enables farmers to receive a diagnosis based on query pictures or the text description of suspicious plants is in high demand for initiating treatment before potential diseases spread further. In this paper, we develop a multimodal plant disease image retrieval system to support disease search based on either image or text prompts. Specifically, we utilize the largest in-the-wild plant disease dataset PlantWild, which includes over 18,000 images across 89 categories, to provide a comprehensive view of potential diseases relating to the query. Furthermore, cross-modal retrieval is achieved in the developed system, facilitated by a novel CLIP-based vision-language model that encodes both disease descriptions and disease images into the same latent space. Built on top of the retriever, our retrieval system allows users to upload either plant disease images or disease descriptions to retrieve the corresponding images with similar characteristics from the disease dataset to suggest candidate diseases for end users' consideration.

Guy Elisha, Sourav Halder, Xinyi Liu et al.

An understanding how neurological disorders lead to mechanical dysfunction of the esophagus requires knowledge of the neural circuit of the enteric nervous system. Historically, this has been elusive. Here, we present an empirically guided neural circuit for the esophagus. It has a chain of unidirectionally coupled relaxation oscillators, receiving excitatory signals from stretch receptors along the esophagus. The resulting neuromechanical model reveals complex patterns and behaviors that emerge from interacting components in the system. A wide variety of clinically observed normal and abnormal esophageal responses to distension are successfully predicted. Specifically, repetitive antegrade contractions (RACs) are conclusively shown to emerge from the coupled neuromechanical dynamics in response to sustained volumetric distension. Normal RACs are shown to have a robust balance between excitatory and inhibitory neuronal populations, and the mechanical input through stretch receptors. When this balance is affected, contraction patterns akin to motility disorders are observed. For example, clinically observed repetitive retrograde contractions emerge due to a hyper stretch sensitive wall. Such neuromechanical insights could be crucial to eventually develop targeted pharmacological interventions.

Yiyang Zhou, Wei Lin, T. Rao et al.

Abstract Ferroptosis is a novel regulated cell death characterized by metabolic disorders and iron-dependent oxidative destruction of the lipid bilayer. It is primarily caused by the imbalance of oxidation and anti-oxidation in the body and is precisely regulated by numerous factors and pathways inside and outside the cell. Recent studies have indicated that ferroptosis plays a vital role in the pathophysiological process of multiple systems of the body including the nervous system. Ferroptosis may be closely linked to the occurrence and development of neurodegenerative diseases, strokes, and brain tumors. It may also be involved in the development, maturation, and aging of the nervous system. Therefore, this study aims to investigate ferroptosis’s occurrence and regulatory mechanism and summarize its research progress in the pathogenesis and treatment of neurological diseases. This would allow for novel ideas for basic and clinical research of neurological diseases.

R. Keikha, S.M. Hashemi-Shahri, A. Jebali

Introduction: The expression of specific miRNAs and their mRNA targets are changed in infectious disease. The aim of this study was to analyze the expression of pro-neuroinflammatory miRNAs, anti-neuroinflammatory miRNAs, and their mRNA targets in the serum of COVID-19 patients with different grades. Methods: COVID-19 patients with different grades were enrolled in this study and the expression of pro-neuroinflammatory miRNAs, anti-neuroinflammatory miRNAs, and their target mRNAs was analyzed by q-PCR. Results: The relative expression of anti- neuroinflammatory miRNAs (mir-21, mir-124, and mir-146a) was decreased and the relative expression of their target mRNAs (IL-12p53, Stat3, and TRAF6) was increased. Also, the relative expression of pro-neuroinflammatory miRNAs (mir-326, mir-155, and mir-27b) was increased and the relative expression of their target mRNA (PPARS, SOCS1, and CEBPA) was decreased in COVID-19 patients with increase of disease grade. A negative significant correlation was seen between mir-21 and IL-12p53 mRNA, mir-124 and Stat3 mRNA, mir-146a and TRAF6 mRNA, mir-27b and PPARS mRNA, mir-155 and SOCS1 mRNA, and between mir-326 and CEBPA mRNA in COVID-19 patients (P < 0.05). Conclusions: This study showed that the relative expression of anti- neuroinflammatory miRNAs was decreased and the relative expression of their targeted mRNAs was increased in COVID-19 patients from asymptomatic to critical illness. Also, this study showed that the relative expression of pro-neuroinflammatory miRNAs was increased and the relative expression of their targeted mRNA was decreased in COVID-19 patients from asymptomatic to critical illness. Resumen: Introducción: La expresión de miARN específicos y sus dianas de ARNm se modifican en las enfermedades infecciosas. El objetivo de este estudio fue analizar la expresión de miARN pro-neuroinflamatorios, miARN anti-neuroinflamatorios y sus ARNm dianas en el suero de pacientes con COVID-19 de diferentes grados. Métodos: Se incluyeron en este estudio pacientes con COVID-19 de diferentes grados y se analizó la expresión de miARN pro-neuroinflamatorios, miARN anti-neuroinflamatorios y sus ARNm diana mediante q-PCR. Resultados: La expresión relativa de miARN anti-neuroinflamatorios (mir-21, mir-124 y mir-146a) disminuyó y la expresión relativa de sus ARNm diana (IL-12p53, Stat3 y TRAF6) aumentó. Además, la expresión relativa de miARN pro-neuroinflamatorios (mir-326, mir-155 y mir-27b) aumentó y la expresión relativa de su ARNm diana (PPARS, SOCS1 y CEBPA) disminuyó en pacientes con COVID-19 con aumento del grado de enfermedad. Se observó una correlación negativa significativa entre ARNm de mir-21 e IL-12p53, ARNm de mir-124 y Stat3, ARNm de mir-146a y TRAF6, ARNm de mir-27b y PPARS, ARNm de mir-155 y SOCS1, y entre mir-326 y ARNm de CEBPA en pacientes con COVID-19 (p < 0,05). Conclusiones: Este estudio mostró que la expresión relativa de miARN anti-neuroinflamatorios disminuyó y la expresión relativa de sus ARNm diana se incrementó en pacientes con COVID-19 de enfermedad asintomática a crítica. Además, este estudio mostró que la expresión relativa de miARN pro-neuroinflamatorios aumentó y la expresión relativa de su ARNm diana disminuyó en pacientes con COVID-19 de enfermedad asintomática a crítica.