470 results
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2. Human CNS-associated macrophages decoded in time and space.
- Subjects
- Humans, Microglia, Macrophages, Central Nervous System
- Published
- 2024
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3. Self-assembled dipeptide grafted nanohybrid material strips for reliable spectroscopic and electrochemical recognition of tryptamine.
- Author
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Divya, Saini, Sanjeev, Kalra, Sanchit, Kaur, Navneet, and Singh, Narinder
- Subjects
- *
TRYPTAMINE , *DIPEPTIDES , *FOODBORNE diseases , *BIOGENIC amines , *CENTRAL nervous system - Abstract
According to the World Health Organization (WHO), foods high in tryptamine may cause foodborne diseases and abnormal activity in the central nervous system (CNS). The real-time monitoring of tryptamine levels is an emphasized topic among scientific community. In the present work, we report a cost-effective fluorescent paper strips-based methodology impregnated with self-assembled dipeptide-modified (DM1) zinc oxide (ZnO) i.e. DM1@ZnO for the real-time monitoring of tryptamine levels. It is based on an organic-inorganic nanohybrid material of self-assembled N -functionalised dipeptide molecule coated over the surface of ZnO thus tailoring its properties for the detection of tryptamine employing spectroscopic and electrochemical methods. The designed material exhibited a noteworthy response towards tryptamine irrespective of the presence of other biogenic amines (BAs). It selectively displayed blue fluorescence under the 365 nm UV light. On top of that, the detection of tryptamine was also corroborated by its transition to 2-oxytryptamine, as deduced from its electrochemical route. Thus, the proposed paper strip-based methodology unbolts a realistic platform for the efficient recognition of varying levels of tryptamine thus tackling the prima facie reasons for foodborne diseases. [Display omitted] • Fabrication of self-assembled dipeptide-based nanohybrid material. • Spectroscopic and electrochemical recognition of tryptamine. • Interaction of DM1@ZnO with tryptamine and its electrochemical conversion to 2-oxytryptamine. • Fabrication of DM1@ZnO grafted fluorescent paper strips. • Realistic platform for the efficient recognition of tryptamine thus tackling the prima facie reasons for foodborne diseases. [ABSTRACT FROM AUTHOR]
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- 2024
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- View/download PDF
4. Nasal Drug Delivery and Nose-to-Brain Delivery Technology Development Status and Trend Analysis: Based on Questionnaire Survey and Patent Analysis.
- Author
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Ge, Yuanyuan, Xu, Xingying, Cao, Meng, Liu, Baijun, Wang, Ying, Liao, Ping, Wang, Jiajing, Chen, Yifei, Yuan, Hongmei, and Chen, Guiliang
- Subjects
INTRANASAL administration ,PATENT applications ,CENTRAL nervous system ,TREND analysis ,RESEARCH personnel - Abstract
Nasal administration is a non-invasive method of drug delivery that offers several advantages, including rapid onset of action, ease of use, no first-pass effect, and fewer side effects. On this basis, nose-to-brain delivery technology offers a new method for drug delivery to the brain and central nervous system, which has attracted widespread attention. In this paper, the development status and trends of nasal drug delivery and nose-to-brain delivery technology are deeply analyzed through multiple dimensions: literature research, questionnaire surveys, and patent analysis. First, FDA-approved nasal formulations for nose-to-brain delivery were combed. Second, we collected a large amount of relevant information about nasal drug delivery through a questionnaire survey of 165 pharmaceutical industry practitioners in 28 provinces and 161 different organizations in China. Third, and most importantly, we conducted a patent analysis of approximately 700+ patents related to nose-to-brain delivery, both domestically and internationally. This analysis was conducted in terms of patent application trends, technology life cycle, technology composition, and technology evolution. The LDA topic model was employed to identify technological topics in each time window (1990–2023), and the five key major evolution paths were extracted. The research results in this paper will provide useful references for relevant researchers and enterprises in the pharmaceutical industry, promoting the further development and application of nasal drug delivery and nose-to-brain delivery technology. [ABSTRACT FROM AUTHOR]
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- 2024
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5. Diagnostic effectiveness of deep learning-based MRI in predicting multiple sclerosis: A meta-analysis.
- Author
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Daqqaq, Tareef S., Alhasan, Ayman S., and Ghunaim, Hadeel A.
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DEEP learning ,MULTIPLE sclerosis ,MAGNETIC resonance imaging ,CONVOLUTIONAL neural networks ,CENTRAL nervous system ,SPINAL cord - Abstract
Copyright of Neurosciences is the property of Neurosciences and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
- Published
- 2024
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6. Trehalose-based coacervates for local bioactive protein delivery to the central nervous system.
- Author
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Hassan LF, Sen R, and O'Shea TM
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- Animals, Mice, Drug Delivery Systems, Mice, Inbred C57BL, Proteins chemistry, Trehalose chemistry, Central Nervous System metabolism, Central Nervous System drug effects
- Abstract
Therapeutic outcomes of local biomolecule delivery to the central nervous system (CNS) using bulk biomaterials are limited by inadequate drug loading, neuropil disruption, and severe foreign body responses. Effective CNS delivery requires addressing these issues and developing well-tolerated, highly-loaded carriers that are dispersible within local neural parenchyma. Here, we synthesized biodegradable trehalose-based polyelectrolyte oligomers using facile A2:B3:AR thiol-ene Michael addition reactions that form complex coacervates upon mixing of oppositely charged oligomers. Coacervates permit high concentration loading and controlled release of bioactive growth factors, enzymes, and antibodies, with modular formulation parameters that confer tunable release kinetics. Coacervates are cytocompatible with cultured neural cells in vitro and can be formulated to either direct intracellular protein delivery or sequester media containing proteins and remain extracellular. Coacervates serve as effective vehicles for precisely delivering biomolecules, including bioactive neurotrophins, to the mouse striatum following intraparenchymal injection. These results support the use of trehalose-based coacervates as part of therapeutic protein delivery strategies for CNS disorders., Competing Interests: Declaration of competing interest Timothy O’Shea reports financial support was provided by Wings for Life Spinal Cord Research Foundation. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)
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- 2024
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7. A Disintegrin And Metalloprotease 10 expression within the murine central nervous system.
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Padilla-Ferrer A, Carrete A, Simon A, Meffre D, and Jafarian-Tehrani M
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- Animals, Mice, Amyloid Precursor Protein Secretases metabolism, Astrocytes metabolism, Microglia metabolism, Cells, Cultured, Oligodendroglia metabolism, Male, Brain metabolism, Cerebellum metabolism, ADAM10 Protein metabolism, Mice, Inbred C57BL, Neurons metabolism, Membrane Proteins metabolism, Central Nervous System metabolism, Spinal Cord metabolism
- Abstract
A Disintegrin And Metalloprotease 10 (ADAM10), is able to control several important physiopathological processes through the shedding of a large number of protein substrates. Although ADAM10 plays a crucial role in the central nervous system (CNS) development and function, its protein distribution in the CNS has not been fully addressed. Here, we described the regional and cellular ADAM10 protein expression in C57BL/6 mice examined by immunofluorescence 1) throughout the adult mouse brain, cerebellum and spinal cord in vivo and 2) in different cell types as neurons, astrocytes, oligodendrocytes and microglia in vitro. We observed ADAM10 expression through the whole CNS, with a strong expression in the hippocampus, in the hypothalamus and in the cerebral and piriform cortex in the brain, in the Purkinje and in granular cell layers in the cerebellum and in the spinal cord to a lower extent. In vivo, ADAM10 protein expression was mainly found in neurons and in some oligodendroglial cell populations. However, in primary cultures we observed ADAM10 expression in neurons, oligodendrocytes, astrocytes and microglia. Interestingly, ADAM10 was not only found in the membrane but also in cytoplasmic vesicles and in the nucleus of primary cultured cells. Overall, this work highlights a wide distribution of ADAM10 throughout the CNS. The nuclear localization of ADAM10, probably due to its intracellular domain, emphasizes its role in cell signalling in physiological and pathological conditions. Further investigations are required to better elucidate the role of ADAM10 in glial cells., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)
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- 2024
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8. Aided Diagnosis Model Based on Deep Learning for Glioblastoma, Solitary Brain Metastases, and Primary Central Nervous System Lymphoma with Multi-Modal MRI.
- Author
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Liu, Xiao and Liu, Jie
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DEEP learning ,CENTRAL nervous system ,CENTRAL nervous system tumors ,CINGULATE cortex ,CANCER diagnosis ,DIAGNOSIS ,MAGNETIC resonance imaging - Abstract
Simple Summary: Diagnosing glioblastoma multiforme (GBM), solitary brain metastases (SBM), and primary central nervous system lymphoma (PCNSL) in malignant tumors of the central nervous system using multi-modal magnetic resonance imaging (MRI) is significantly important in helping physicians develop treatment plans and enhance patient prognosis. In this paper, MFFC-Net is developed and validated using deep learning methods to predict these three tumor categories from multi-modal MRI without the manual region of interest (ROI). MFFC-Net first uses a multi-encoder with DenseBlocks to extract deep features from multi-modal MRI. Then, the feature fusion layer fuses the deep information between different modalities and tissues. Finally, the spatial-channel attention module suppresses redundant new information and activates tumor classification-related features. Compared with radiomics models, MFFC-Net demonstrated higher accuracy. In addition, the results in the different sequences provide important references for future clinical work on MRI image acquisition. We believe that MFFC-Net has the potential to assist in the diagnosis and treatment of brain tumors in the future. (1) Background: Diagnosis of glioblastoma (GBM), solitary brain metastases (SBM), and primary central nervous system lymphoma (PCNSL) plays a decisive role in the development of personalized treatment plans. Constructing a deep learning classification network to diagnose GBM, SBM, and PCNSL with multi-modal MRI is important and necessary. (2) Subjects: GBM, SBM, and PCNSL were confirmed by histopathology with the multi-modal MRI examination (study from 1225 subjects, average age 53 years, 671 males), 3.0 T T2 fluid-attenuated inversion recovery (T2-Flair), and Contrast-enhanced T1-weighted imaging (CE-T1WI). (3) Methods: This paper introduces MFFC-Net, a classification model based on the fusion of multi-modal MRIs, for the classification of GBM, SBM, and PCNSL. The network architecture consists of parallel encoders using DenseBlocks to extract features from different modalities of MRI images. Subsequently, an L 1 − n o r m feature fusion module is applied to enhance the interrelationships among tumor tissues. Then, a spatial-channel self-attention weighting operation is performed after the feature fusion. Finally, the classification results are obtained using the full convolutional layer (FC) and Soft-max. (4) Results: The ACC of MFFC-Net based on feature fusion was 0.920, better than the radiomics model (ACC of 0.829). There was no significant difference in the ACC compared to the expert radiologist (0.920 vs. 0.924, p = 0.774). (5) Conclusions: Our MFFC-Net model could distinguish GBM, SBM, and PCNSL preoperatively based on multi-modal MRI, with a higher performance than the radiomics model and was comparable to radiologists. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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9. The Electromagnetic Exposure Level of a Pure Electric Vehicle Inverter Based on a Real Human Body.
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Dong, Xuwei, Gao, Yunshan, and Lu, Mai
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ELECTRIC inverters ,HUMAN body ,HUMAN anatomy ,MAGNETIC flux density ,HEART ,ORGANS (Anatomy) ,CENTRAL nervous system - Abstract
In order to quantitatively analyze the electromagnetic exposure dose of an inverter in a pure electric vehicle to the driver's body and assess the safety of the electromagnetic exposure, based on a real human anatomy model in the virtual home project, a real human model with several organs and tissues, including muscles, bones, a heart, lungs, a liver, kidneys, a bladder, a skull, a scalp, white matter, and a cerebellum, was constructed. The inverter of a pure electric vehicle is considered to be the electromagnetic exposure source; for this study, an equivalent electromagnetic environment model composed of a real human body, an inverter, and a vehicle body was built. The distribution of induced fields in the driver's tissues and organs was calculated and analyzed using the finite element method. The results show that the distribution of the magnetic flux density, induced electric field, and induced current density in the driver's body was affected by the spatial distance of the inverter. The farther the distance was, the weaker the value was. Specifically, due to the different dielectric properties of the different tissues, the induced field in the different tissues was significantly different. However, the maximum magnetic flux density over the space occupied by the driver's body and induced electric field in the driver's trunk and central nervous system satisfied the exposure limits of the International Commission on Non-Ionization Radiation Protection, indicating that the electromagnetic environments generated by the inverter proposed in this paper are safe for the vehicle driver's health. The numerical results of this study could also effectively supplement the study of the electromagnetic environments of pure electric vehicles and provide some references for protecting the drivers of pure electric vehicles from electromagnetic radiation. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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10. The role of annexins in central nervous system development and disease.
- Author
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White ZB 2nd, Nair S, and Bredel M
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- Humans, Animals, Blood-Brain Barrier metabolism, Central Nervous System Diseases metabolism, Central Nervous System Diseases pathology, Central Nervous System Neoplasms metabolism, Central Nervous System Neoplasms pathology, Annexins metabolism, Central Nervous System metabolism
- Abstract
Annexins, a group of Ca
2+ -dependent phospholipid-binding proteins, exert diverse roles in neuronal development, normal central nervous system (CNS) functioning, neurological disorders, and CNS tumors. This paper reviews the roles of individual annexins (A1-A13) in these contexts. Annexins possess unique structural and functional features, such as Ca2+ -dependent binding to phospholipids, participating in membrane organization, and modulating cell signaling. They are implicated in various CNS processes, including endocytosis, exocytosis, and stabilization of plasma membranes. Annexins exhibit dynamic roles in neuronal development, influencing differentiation, proliferation, and synaptic formation in CNS tissues. Notably, annexins such as ANXA1 and ANXA2 play roles in apoptosis and blood-brain barrier (BBB) integrity. Neurological disorders, including Alzheimer's disease, multiple sclerosis, and depression, involve annexin dysregulation, influencing neuroinflammation, blood-brain barrier integrity, and stress responses. Moreover, annexins contribute to the pathogenesis of CNS tumors, either promoting or suppressing tumor growth, angiogenesis, and invasion. Annexin expression patterns vary across different CNS tumor types, providing potential prognostic markers and therapeutic targets. This review underscores the multifaceted roles of annexins in the CNS, highlighting their importance in normal functioning, disease progression, and potential therapeutic interventions., (© 2024. The Author(s).)- Published
- 2024
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11. The effects of micro- and nanoplastics on the central nervous system: A new threat to humanity?
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Zheng Y, Xu S, Liu J, and Liu Z
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- Animals, Humans, Blood-Brain Barrier drug effects, Blood-Brain Barrier metabolism, Neurotoxicity Syndromes etiology, Central Nervous System drug effects, Microplastics toxicity, Nanoparticles toxicity
- Abstract
Given the widespread production and use of plastics, poor biodegradability, and inadequate recycling, micro/nanoplastics (MNPs) have caused widespread environmental pollution. As a result, humans inevitably ingest MNPs through various pathways. However, there is still no consensus on whether exposure to MNPs has adverse effects on humans. This article aims to provide a comprehensive overview of the knowledge of MNPs and the potential mechanisms of their impact on the central nervous system. Numerous in vivo and in vitro studies have shown that exposure to MNPs may pass through the blood-brain barrier (BBB) and lead to neurotoxicity through impairments in oxidative and inflammatory balance, neurotransmitter alternation, nerve conduction-related key enzymes, and impact through the gut-brain axis. It is worth noting that MNPs may act as carriers and have more severe effects on the body when co-exposed with other substances. MNPs of smaller sizes cause more severe harm. Despite the scarcity of reports directly relevant to humans, this review brings together a growing body of evidence showing that exposure to MNPs disturbs neurons and has even been found to alter the memory and behavior of organisms. This effect may lead to further potential negative influence on the central nervous system and contribute to the development of other diseases such as central nervous system inflammation and Parkinson 's-like neurodegenerative disorders. There is a need further to investigate the threat of MNPs to human health., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
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- 2024
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12. Research progress on the regulation of intestinal flora on glioma.
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XI Kexin, ZHAO Yuqi, XIE Xiaoting, LU Yuntao, FAN Hongying, and HE Xiaoyan
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GLIOMAS ,BOTANY ,INTESTINES ,CENTRAL nervous system ,GUT microbiome ,BRAIN tumors - Abstract
Glioma is the most common primary tumor of the brain, accounting for 81 % of central nervous system (CNS) malignant tumors. The degree of malignancy is high, and the current treatment methods are limited. In recent years, with the in-depth study of intestinal flora and brain-gut axis, it has been found that the diversity of gut microbiota plays an important role in the regulation of glioma. The mechanism is that the intestinal flora affects the development of glioma through the role of immune regulation and metabolites. In addition, it has been confirmed that there is a certain correlation between some probiotics and glioma, which provides a new application prospect for the treatment of glioma. This paper discusses the main intestinal bacteria that regulate gliomas as well as the role and regulatory mechanisms of intestinal flora in the development of gliomas, and provides ideas for the discovery of new targets for glioma treatment and further improvement of treatment options. [ABSTRACT FROM AUTHOR]
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- 2024
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13. Inner Structure of the Lateral Geniculate Complex of Adult and Newborn Acomys cahirinus.
- Author
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Merkulyeva, Natalia, Mikhalkin, Aleksandr, and Veshchitskii, Aleksandr
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LATERAL geniculate body ,CALCIUM-binding proteins ,GLUTAMATE decarboxylase ,NEWBORN infants ,ADULTS ,CENTRAL nervous system - Abstract
Acomys cahirinus is a unique Rodentia species with several distinctive physiological traits, such as precocial development and remarkable regenerative abilities. These characteristics render A. cahirinus increasingly valuable for regenerative and developmental physiology studies. Despite this, the structure and postnatal development of the central nervous system in A. cahirinus have been inadequately explored, with only sporadic data available. This study is the first in a series of papers addressing these gaps. Our first objective was to characterize the structure of the main visual thalamic region, the lateral geniculate complex, using several neuronal markers (including Ca
2+ -binding proteins, glutamic acid decarboxylase enzyme, and non-phosphorylated domains of heavy-chain neurofilaments) to label populations of principal neurons and interneurons in adult and newborn A. cahirinus. As typically found in other rodents, we identified three subdivisions in the geniculate complex: the dorsal and ventral lateral geniculate nuclei (LGNd and LGNv) and the intergeniculate leaflet (IGL). Additionally, we characterized internal diversity in the LGN nuclei. The "shell" and "core" regions of the LGNd were identified using calretinin in adults and newborns. In adults, the inner and outer parts of the LGNv were identified using calbindin, calretinin, parvalbumin, GAD67, and SMI-32, whereas in newborns, calretinin and SMI-32 were employed for this purpose. Our findings revealed more pronounced developmental changes in LGNd compared to LGNv and IGL, suggesting that LGNd is less mature at birth and more influenced by visual experience. [ABSTRACT FROM AUTHOR]- Published
- 2024
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14. Electroencephalographic insights into the pathophysiological mechanisms of emergence delirium in children and corresponding clinical treatment strategies.
- Author
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Xin Gao, Zhichao Li, Jun Chai, Si Li, Xuanyuan Pan, Jie Liu, Linxing Li, Shangyuan Qin, Yihan Kang, and Youzhuang Zhu
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DELIRIUM ,ELECTROENCEPHALOGRAPHY ,INHALATION anesthetics ,CENTRAL nervous system ,DRUG therapy ,NEUROPHYSIOLOGY - Abstract
Emergence delirium is a common postoperative complication in patients undergoing general anesthesia, especially in children. In severe cases, it can cause unnecessary self-harm, affect postoperative recovery, lead to parental dissatisfaction, and increase medical costs. With the widespread use of inhalation anesthetic drugs (such as sevoflurane and desflurane), the incidence of emergence delirium in children is gradually increasing; however, its pathogenesis in children is complex and unclear. Several studies have shown that age, pain, and anesthetic drugs are strongly associated with the occurrence of emergence delirium. Alterations in central neurophysiology are essential intermediate processes in the development of emergence delirium. Compared to adults, the pediatric nervous system is not fully developed; therefore, the pediatric electroencephalogram may vary slightly by age. Moreover, pain and anesthetic drugs can cause changes in the excitability of the central nervous system, resulting in electroencephalographic changes. In this paper, we review the pathogenesis of and prevention strategies for emergence delirium in children from the perspective of brain electrophysiology--especially for commonly used pharmacological treatments--to provide the basis for understanding the development of emergence delirium as well as its prevention and treatment, and to suggest future research direction. [ABSTRACT FROM AUTHOR]
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- 2024
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15. Neuroinfectious Diseases in Children: Pathophysiology, Outcomes, and Global Challenges.
- Author
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Huff HV and Wilson-Murphy M
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- Child, Humans, Brain, Central Nervous System, Blood-Brain Barrier
- Abstract
Pathogens with affinity for the central nervous system (CNS) in children are diverse in their mechanisms of infecting and attacking the brain. Infections can reach the CNS via hematogenous routes, transneurally thereby avoiding the blood-brain barrier, and across mucosal or skin surfaces. Once transmission occurs, pathogens can wreak havoc both by direct action on host cells and via an intricate interplay between the protective and pathologic actions of the host's immune system. Pathogen prevalence varies depending on region, and susceptibility differs based on epidemiologic factors such as age, immune status, and genetics. In addition, some infectious diseases are monophasic, whereas others may lie dormant for years, thereby causing a dynamic effect on outcomes. Outcomes in survivors are highly variable for each particular pathogen and depend on the vaccination and immune status of the patient as well as the speed by which the patient receives evidence-based treatments. Given pathogens cause communicable diseases that can cause morbidity and mortality on a population level when spread, the burden is often the greatest and the outcomes the worst in low-resource settings. Here we will focus on the most common infections with a propensity to affect a child's brain, the pathologic mechanisms by which they do so, and what is known about the developmental outcomes in children who are affected by these infections., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)
- Published
- 2024
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16. Case report: Overlap syndrome of neuromyelitis optica spectrum disorder with anti-Argonaute antibodies.
- Author
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Pei Liu, Xuemei Lin, and Songdi Wu
- Subjects
NEUROMYELITIS optica ,SYMPTOMS ,TRANSVERSE myelitis ,PROGNOSIS ,CENTRAL nervous system ,IMMUNOGLOBULINS - Abstract
Aquaporin-4 antibodies (AQP4-Abs) are a diagnostic marker for patients with a demyelinating disease called neuromyelitis optica spectrum disorder (NMOSD). Anti-Argonaute antibodies (AGO-Abs) present as potential biomarkers of the overlap syndrome between NMOSD and other autoimmune diseases. In this paper, we present the case of an adult woman with numbness, tingling, and burning sensations in her arms and subsequent bilateral internuclear ophthalmoplegia. Brain–cervical–thoracic magnetic resonance imaging (MRI) showed T2 hyperintensities in the dorsal brainstem and around the midbrain aqueduct and longitudinally transverse myelitis with homogeneous enhancement on gadolinium-enhanced MRI. The contemporaneous detection of AQP4- and AGO-Abs led to a definite diagnosis of overlap syndrome of NMOSD with AGO-Abs. The patient was treated with immunosuppressive agents, including corticosteroids and immunoglobulins, and achieved remission. This case highlights a novel phenotype of NMOSD with AGO-Abs overlap syndrome, which presents with relapsing brainstem syndrome and longitudinally extensive myelitis with acute severe neurological involvement. The promising prognosis of the disease could serve as a distinct clinical profile. Broad screening for antibodies against central nervous system autoimmune antigens is recommended in suspected patients with limited or atypical clinical manifestations. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
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17. Is blood pTau a reliable indicator of the CSF status? A narrative review.
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Antonioni, Annibale, Raho, Emanuela Maria, and Di Lorenzo, Francesco
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- *
ALZHEIMER'S disease , *LITERATURE reviews , *TAU proteins , *NEUROFIBRILLARY tangles , *CENTRAL nervous system - Abstract
Background: The identification of biomarkers for the early diagnosis of Alzheimer's disease (AD) is a crucial goal of the current research. Blood biomarkers are less invasive, easier to obtain and achievable by a cheaper means than those on cerebrospinal fluid (CSF) and significantly more economic than functional neuroimaging investigations; thus, a great interest is focused on blood isoforms of the phosphorylated Tau protein (pTau), indicators of ongoing tau pathology (i.e. neurofibrillary tangles, NFTs, an AD neuropathological hallmark) in the central nervous system (CNS). However, current data often highlight discordant results about the ability of blood pTau to predict CSF status. Objective: We aim to synthesise the studies that compared pTau levels on CSF and blood to assess their correlation in AD continuum. Methods: We performed a narrative literature review using, first, MEDLINE (via PubMed) by means of MeSH terms, and then, we expanded the reults by means of Scopus and Web of Sciences to be as inclusive as possible. Finally, we added work following an expert opinion. Only papers presenting original data on pTau values on both blood and CSF were included. Results: The 33 included studies show an extreme heterogeneity in terms of pTau isoform (pTau181, 217 and 231), laboratory methods, diagnostic criteria and choice of comparison groups. Most studies evaluated plasma pTau181, while data on other isoforms and serum are scarcer. Discussion: Most papers identify a correlation between CSF and blood measurements. Furthermore, even when not specified, it is often possible to show an increase in blood pTau values as AD-related damage progresses in the AD continuum and higher values in AD than in other neurodegenerative diseases. Notably, plasma pTau231 seems the first biomarker to look for in the earliest and pre-clinical stages, quickly followed by pTau217 and, finally, by pTau181. Conclusions: Our results encourage the use of blood pTau for the early identification of patients with AD continuum. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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18. A primer to vascular anatomy of the brain: an overview on anterior compartment.
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Morales-Roccuzzo, Diego, Sabahi, Mohammadmahdi, Obrzut, Michal, Najera, Edinson, Monterroso-Cohen, David, Bsat, Shadi, Adada, Badih, and Borghei-Razavi, Hamid
- Subjects
- *
BRAIN anatomy , *INTERNAL carotid artery , *ANTERIOR cerebral artery , *LITERATURE reviews , *VERTEBRAL artery , *CENTRAL nervous system - Abstract
Purpose: Knowledge of neurovascular anatomy is vital for neurosurgeons, neurologists, neuro-radiologists and anatomy students, amongst others, to fully comprehend the brain's anatomy with utmost depth. This paper aims to enhance the foundational knowledge of novice physicians in this area. Method: A comprehensive literature review was carried out by searching the PubMed and Google Scholar databases using primary keywords related to brain vasculature, without date restrictions. The identified literature was meticulously examined and scrutinized. In the process of screening pertinent papers, further articles and book chapters were obtained through analysis and additional assessing of the reference lists. Additionally, four formalin-fixed, color latex-injected cadaveric specimens preserved in 70% ethanol solution were dissected under surgical microscope (Leica Microsystems Inc, 1700 Leider Ln, Buffalo Grove, IL 60089 USA). Using microneurosurgical as well as standard instruments, and a high-speed surgical drill (Stryker Instruments 1941 Stryker Way Portage, MI 49002 USA). Ulterior anatomical dissection was documented in microscopic images. Results: Encephalic circulation functions as a complex network of intertwined vessels. The Internal Carotid Arteries (ICAs) and the Vertebral Arteries (VAs), form the anterior and posterior arterial circulations, respectively. This work provides a detailed exploration of the neurovascular anatomy of the anterior circulation and its key structures, such as the Anterior Cerebral Artery (ACA) and the Middle Cerebral Artery (MCA). Embryology is also briefly covered, offering insights into the early development of the vascular structures of the central nervous system. Cerebral venous system was detailed, highlighting the major veins and tributaries involved in the drainage of blood from the intracranial compartment, with a focus on the role of the Internal Jugular Veins (IJVs) as the primary, although not exclusive, deoxygenated blood outflow pathway. Conclusion: This work serves as initial guide, providing essential knowledge on neurovascular anatomy, hoping to reduce the initial impact when tackling the subject, albeit the intricate vasculature of the brain will necessitate further efforts to be conquered, that being crucial for neurosurgical and neurology related practice and clinical decision-making. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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19. Central precocious puberty - etiology with particular consideration of neurological causes.
- Author
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Gracjasz-Palikij, Izabela, Paprocka, Justyna, and Gawlik, Aneta
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PRECOCIOUS puberty ,DISEASE risk factors ,CENTRAL nervous system ,ETIOLOGY of diseases ,HYPOTHALAMIC-pituitary-gonadal axis ,RARE diseases - Abstract
Central precocious puberty (CPP) is a rare disease of poorly understood etiology. The cause is mostly idiopathic. However, congenital and acquired structural changes in the central nervous system are also involved. Prevalent organic changes in the central nervous system, especially among boys, prompt imaging assessment in each case of CPP. In addition, genetic and environmental factors have been reported. Safe and effective treatment is available. The time of treatment implementation is crucial to the successful outcome. Proper diagnosis and treatment make it possible to avoid a number of complications of untreated CPP. There are only a few studies analyzing the prevalence and risk factors for the disease. The aim of this paper is to discuss the current causes of CPP with particular consideration of neurological aspects. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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20. New Heterostilbene and Triazole Oximes as Potential CNS-Active and Cholinesterase-Targeted Therapeutics.
- Author
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Mlakić, Milena, Čadež, Tena, Šinko, Goran, Škorić, Irena, and Kovarik, Zrinka
- Subjects
OXIMES ,OXIME derivatives ,BLOOD-brain barrier ,PARKINSON'S disease ,TRIAZOLES ,ORGANOPHOSPHORUS compounds ,CENTRAL nervous system - Abstract
New furan, thiophene, and triazole oximes were synthesized through several-step reaction paths to investigate their potential for the development of central nervous systems (CNS)-active and cholinesterase-targeted therapeutics in organophosphorus compound (OP) poisonings. Treating patients with acute OP poisoning is still a challenge despite the development of a large number of oxime compounds that should have the capacity to reactivate acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The activity of these two enzymes, crucial for neurotransmission, is blocked by OP, which has the consequence of disturbing normal cholinergic nerve signal transduction in the peripheral and CNS, leading to a cholinergic crisis. The oximes in use have one or two pyridinium rings and cross the brain–blood barrier poorly due to the quaternary nitrogen. Following our recent study on 2-thienostilbene oximes, in this paper, we described the synthesis of 63 heterostilbene derivatives, of which 26 oximes were tested as inhibitors and reactivators of AChE and BChE inhibited by OP nerve agents–sarin and cyclosarin. While the majority of oximes were potent inhibitors of both enzymes in the micromolar range, we identified several oximes as BChE or AChE selective inhibitors with the potential for drug development. Furthermore, the oximes were poor reactivators of AChE; four heterocyclic derivatives reactivated cyclosarin-inhibited BChE up to 70%, and cis,trans-5 [2-((Z)-2-(5-((E)-(hydroxyimino)methyl)thiophen-2-yl)vinyl)benzonitrile] had a reactivation efficacy comparable to the standard oxime HI-6. In silico analysis and molecular docking studies, including molecular dynamics simulation, connected kinetic data to the structural features of these oximes and confirmed their productive interactions with the active site of cyclosarin-inhibited BChE. Based on inhibition and reactivation and their ADMET properties regarding lipophilicity, CNS activity, and hepatotoxicity, these compounds could be considered for further development of CNS-active reactivators in OP poisoning as well as cholinesterase-targeted therapeutics in neurodegenerative diseases such as Alzheimer's and Parkinson's. [ABSTRACT FROM AUTHOR]
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- 2024
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21. Optical Devices for the Diagnosis and Management of Spinal Cord Injuries: A Review.
- Author
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Sharma, Sonika, Kalyani, Neeti, Dutta, Taposhree, Velázquez-González, Jesús Salvador, Llamas-Garro, Ignacio, Ung, Bora, Bas, Joan, Dubey, Rakesh, and Mishra, Satyendra K.
- Subjects
SPINAL cord injuries ,OPTICAL devices ,CENTRAL nervous system ,DIAGNOSIS ,SPINAL cord - Abstract
Throughout the central nervous system, the spinal cord plays a very important role, namely, transmitting sensory and motor information inwardly so that it can be processed by the brain. There are many different ways this structure can be damaged, such as through traumatic injury or surgery, such as scoliosis correction, for instance. Consequently, damage may be caused to the nervous system as a result of this. There is no doubt that optical devices such as microscopes and cameras can have a significant impact on research, diagnosis, and treatment planning for patients with spinal cord injuries (SCIs). Additionally, these technologies contribute a great deal to our understanding of these injuries, and they are also essential in enhancing the quality of life of individuals with spinal cord injuries. Through increasingly powerful, accurate, and minimally invasive technologies that have been developed over the last decade or so, several new optical devices have been introduced that are capable of improving the accuracy of SCI diagnosis and treatment and promoting a better quality of life after surgery. We aim in this paper to present a timely overview of the various research fields that have been conducted on optical devices that can be used to diagnose spinal cord injuries as well as to manage the associated health complications that affected individuals may experience. [ABSTRACT FROM AUTHOR]
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- 2024
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22. The Landscape of Pediatric High-Grade Gliomas: The Virtues and Pitfalls of Pre-Clinical Models.
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Furst, Liam M., Roussel, Enola M., Leung, Ryan F., George, Ankita M., Best, Sarah A., Whittle, James R., Firestein, Ron, Faux, Maree C., and Eisenstat, David D.
- Subjects
ANIMAL models in research ,CANCER cell culture ,GLIOMAS ,BRAIN tumors ,GENE expression profiling ,CENTRAL nervous system - Abstract
Simple Summary: Pediatric high-grade gliomas are aggressive and deadly brain tumors that arise in children and are notoriously difficult to cure. Researchers require accurate methods, or "model systems," to better understand these tumors. Model systems include culturing cancer cells in a dish, observing how cancer cells grow in an animal brain, and growing cells in self-organizing 3D cultures called organoids, which more accurately resemble the brain. In this paper, we describe the molecular changes that these cancers acquire that cause them to be so aggressive, the development of past and present model systems, highlight the newest model systems being developed, and offer suggestions regarding how these model systems can be used in the future to develop better therapies for patients. Further, we outline the benefits and limitations of each model system to better guide researchers in the design of their experiments. Developing a variety of model systems that adequately and faithfully represent how tumors exist, progress, recur, and respond to treatment in a patient is absolutely essential to the eventual development of effective therapeutics. Therefore, investing in the continued development of these model systems is paramount to improving patient outcomes. Pediatric high-grade gliomas (pHGG) are malignant and usually fatal central nervous system (CNS) WHO Grade 4 tumors. The majority of pHGG consist of diffuse midline gliomas (DMG), H3.3 or H3.1 K27 altered, or diffuse hemispheric gliomas (DHG) (H3.3 G34-mutant). Due to diffuse tumor infiltration of eloquent brain areas, especially for DMG, surgery has often been limited and chemotherapy has not been effective, leaving fractionated radiation to the involved field as the current standard of care. pHGG has only been classified as molecularly distinct from adult HGG since 2012 through Next-Generation sequencing approaches, which have shown pHGG to be epigenetically regulated and specific tumor sub-types to be representative of dysregulated differentiating cells. To translate discovery research into novel therapies, improved pre-clinical models that more adequately represent the tumor biology of pHGG are required. This review will summarize the molecular characteristics of different pHGG sub-types, with a specific focus on histone K27M mutations and the dysregulated gene expression profiles arising from these mutations. Current and emerging pre-clinical models for pHGG will be discussed, including commonly used patient-derived cell lines and in vivo modeling techniques, encompassing patient-derived xenograft murine models and genetically engineered mouse models (GEMMs). Lastly, emerging techniques to model CNS tumors within a human brain environment using brain organoids through co-culture will be explored. As models that more reliably represent pHGG continue to be developed, targetable biological and genetic vulnerabilities in the disease will be more rapidly identified, leading to better treatments and improved clinical outcomes. [ABSTRACT FROM AUTHOR]
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- 2024
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23. Exosomes in the Diagnosis of Neuropsychiatric Diseases: A Review.
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Wu, Song, Shang, Xinmiao, Guo, Meng, Su, Lei, and Wang, Jun
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EXOSOMES ,DIAGNOSIS ,EXTRACELLULAR vesicles ,LINCRNA ,CENTRAL nervous system - Abstract
Simple Summary: The diagnostic value of exosomes has been well recognized by researchers. The use of exosomal biomarkers as an adjunct diagnosis method not only improves diagnostic accuracy but can also be used for early diagnosis and disease progression differentiation, thus supporting personalized clinical treatment strategies for patients with neuropsychiatric disorders. In this paper, we summarize potential exosomal biomarkers in the diagnosis of neuropsychiatric diseases. Exosomes are 30–150 nm small extracellular vesicles (sEVs) which are highly stable and encapsulated by a phospholipid bilayer. Exosomes contain proteins, lipids, RNAs (mRNAs, microRNAs/miRNAs, long non-coding RNAs/lncRNAs), and DNA of their parent cell. In pathological conditions, the composition of exosomes is altered, making exosomes a potential source of biomarkers for disease diagnosis. Exosomes can cross the blood–brain barrier (BBB), which is an advantage for using exosomes in the diagnosis of central nervous system (CNS) diseases. Neuropsychiatric diseases belong to the CNS diseases, and many potential diagnostic markers have been identified for neuropsychiatric diseases. Here, we review the potential diagnostic markers of exosomes in neuropsychiatric diseases and discuss the potential application of exosomal biomarkers in the early and accurate diagnosis of these diseases. Additionally, we outline the limitations and future directions of exosomes in the diagnosis of neuropsychiatric diseases. [ABSTRACT FROM AUTHOR]
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- 2024
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24. Microbiome-Glia Crosstalk: Bridging the Communication Divide in the Central Nervous System.
- Author
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Tabatabaee, Mitra
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CENTRAL nervous system ,NEUROGLIA ,HUMAN microbiota ,NEUROPLASTICITY ,NEUROLOGICAL disorders - Abstract
The traditional neuron-centric view of the central nervous system (CNS) is shifting toward recognizing the importance of communication between the neurons and the network of glial cells. This shift is leading to a more comprehensive understanding of how glial cells contribute to CNS function. Alongside this shift, recent discoveries have illuminated the significant role of the human microbiome, comprising trillions of microorganisms, mirroring the number of human cells in an individual. This paper delves into the multifaceted functions of neuroglia, or glial cells, which extend far beyond their traditional roles of supporting and protecting neurons. Neuroglia modulate synaptic activity, insulate axons, support neurogenesis and synaptic plasticity, respond to injury and inflammation, and engage in phagocytosis. Meanwhile, the microbiome, long overlooked, emerges as a crucial player in brain functionality akin to glial cells. This review aims to underscore the importance of the interaction between glial cells and resident microorganisms in shaping the development and function of the human brain, a concept that has been less studied. Through a comprehensive examination of existing literature, we discuss the mechanisms by which glial cells interface with the microbiome, offering insights into the contribution of this relationship to neural homeostasis and health. Furthermore, we discuss the implications of dysbiosis within this interaction, highlighting its potential contribution to neurological disorders and paving the way for novel therapeutic interventions targeting both glial cells and the microbiome. [ABSTRACT FROM AUTHOR]
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- 2024
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25. The Emerging Role of Microglial Hv1 as a Target for Immunomodulation in Myelin Repair.
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Yingxin Tang, Xuan Wu, Jiarui Li, Yuanwei Li, Xiaoxiao Xu, Gaigai Li, Ping Zhang, Chuan Qin, Long-Jun Wu, Zhouping Tang, and Dai-Shi Tian
- Subjects
MICROGLIA ,IMMUNOREGULATION ,CENTRAL nervous system - Abstract
In the central nervous system (CNS), the myelin sheath ensures efficient interconnection between neurons and contributes to the regulation of the proper function of neuronal networks. The maintenance of myelin and the well-organized subtle process of myelin plasticity requires cooperation among myelin-forming cells, glial cells, and neural networks. The process of cooperation is fragile, and the balance is highly susceptible to disruption by microenvironment influences. Reactive microglia play a critical and complicated role in the demyelination and remyelination process. Recent studies have shown that the voltage-gated proton channel Hv1 is selectively expressed in microglia in CNS, which regulates intracellular pH and is involved in the production of reactive oxygen species, underlying multifaceted roles in maintaining microglia function. This paper begins by examining the molecular mechanisms of demyelination and emphasizes the crucial role of the microenvironment in demyelination. It focuses specifically on the role of Hv1 in myelin repair and its therapeutic potential in CNS demyelinating diseases. [ABSTRACT FROM AUTHOR]
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- 2024
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26. Multifunctional roles of γ-enolase in the central nervous system: more than a neuronal marker.
- Author
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Horvat, Selena, Kos, Janko, and Pišlar, Anja
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CENTRAL nervous system ,ALZHEIMER'S disease ,SCAFFOLD proteins ,NEURONS ,NEUROLOGICAL disorders - Abstract
Enolase, a multifunctional protein with diverse isoforms, has generally been recognized for its primary roles in glycolysis and gluconeogenesis. The shift in isoform expression from α-enolase to neuron-specific γ-enolase extends beyond its enzymatic role. Enolase is essential for neuronal survival, differentiation, and the maturation of neurons and glial cells in the central nervous system. Neuron-specific γ-enolase is a critical biomarker for neurodegenerative pathologies and neurological conditions, not only indicating disease but also participating in nerve cell formation and neuroprotection and exhibiting neurotrophic-like properties. These properties are precisely regulated by cysteine peptidase cathepsin X and scaffold protein γ
1 -syntrophin. Our findings suggest that γ-enolase, specifically its C-terminal part, may offer neuroprotective benefits against neurotoxicity seen in Alzheimer's and Parkinson's disease. Furthermore, although the therapeutic potential of γ-enolase seems promising, the effectiveness of enolase inhibitors is under debate. This paper reviews the research on the roles of γ-enolase in the central nervous system, especially in pathophysiological events and the regulation of neurodegenerative diseases. [ABSTRACT FROM AUTHOR]- Published
- 2024
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27. Emerging insights into cuproptosis and copper metabolism: implications for age-related diseases and potential therapeutic strategies.
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Haohui Fan, Kun Wang, Xiaofang Zhao, Bei Song, Tianci Yao, Ting Liu, Guangyu Gao, Weilin Lu, and Chengyun Liu
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COPPER metabolism ,PROTEINS ,MUSCULOSKELETAL system ,GLUTATHIONE ,MITOCHONDRIA ,APOPTOSIS ,COPPER ,RETINAL degeneration ,OXIDATIVE stress ,CENTRAL nervous system ,PARKINSON'S disease ,NEURODEGENERATION ,ATHEROSCLEROSIS ,REACTIVE oxygen species ,AMYOTROPHIC lateral sclerosis ,AGING ,GENETIC mutation ,INFLAMMATION ,DIGESTIVE organs ,STROKE ,TRICARBOXYLIC acids ,CARDIOVASCULAR system ,PLANT proteins ,DIABETES ,SARCOPENIA - Abstract
The expanding geriatric population, whose predisposition toward disabling morbidities and age-related diseases (ARD) is well-documented, has become a paramount social issue, exerting an onerous burden on both the healthcare industry and wider society. ARD manifest as the progressive deterioration of bodily tissues and organs, eventually resulting in the failure of these vital components. At present, no efficacious measures exist to hinder the onset of ARD. Copper, an essential trace element, is involved in a wide range of physiological processes across different cell types. In recent research, a novel variant of copper-dependent cell death, termed cuproptosis, has been identified. This mode of cellular demise stands apart from previously recognized types of cell death. Cuproptosis occurs when copper binds with acyl-CoA synthetase in the tricarboxylic acid (TCA) cycle, resulting in protein aggregation and protein toxicity stress, ultimately leading to cell death. In this paper, we provide a concise overview of the current understanding concerning the metabolism of copper, copper-related diseases, the hallmarks of copper toxicity, and the mechanisms that regulate copper toxicity. Additionally, we discuss the implications of cuproptosis mutations in the development of ARD, as well as the potential for targeting cuproptosis as a treatment for ARD. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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28. A Difficult Case of Ventriculitis in a 40-Year-Old Woman with Acute Myeloid Leukemia.
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Rubino, Raffaella, Trizzino, Marcello, Pipitò, Luca, Sucato, Giuseppe, Santoro, Marco, Maugeri, Rosario, Iacopino, Domenico Gerardo, Giammanco, Giovanni Maurizio, Siragusa, Sergio, and Cascio, Antonio
- Subjects
ACUTE myeloid leukemia ,KLEBSIELLA infections ,ENTEROCOCCAL infections ,CENTRAL nervous system infections ,ENTEROCOCCUS faecium ,CENTRAL nervous system ,GRAM-positive bacteria - Abstract
Ventriculitis and nosocomial meningitis caused by carbapenem-resistant Gram-negative and vancomycin-resistant Gram-positive bacteria represent a growing treatment challenge. A case of ventriculitis and bacteremia caused by carbapenem-resistant, KPC-producing Klebsiella pneumoniae and vancomycin-resistant Enterococcus faecium in a young woman with acute leukemia who was successfully treated with meropenem/vaborbactam (MVB), rifampicin, and linezolid is described in this paper. This case report emphasizes the importance of a multidisciplinary strategy, including infectious focus control, for the treatment of device-associated central nervous system (CNS) infections from multidrug-resistant bacteria. Considering the novel resistance patterns, more research on drug penetration into the central nervous system, as well as on the necessity of association therapies, is needed. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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29. HIV-Associated Neurocognitive Disorder: A Look into Cellular and Molecular Pathology.
- Author
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Thompson, Landon John-Patrick, Genovese, Jessica, Hong, Zhenzi, Singh, Meera Vir, and Singh, Vir Bahadur
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NEUROBEHAVIORAL disorders ,CELLULAR pathology ,BLOOD-brain barrier ,TAT protein ,HIV-1 glycoprotein 120 ,MOLECULAR pathology ,CENTRAL nervous system - Abstract
Despite combined antiretroviral therapy (cART) limiting HIV replication to undetectable levels in the blood, people living with HIV continue to experience HIV-associated neurocognitive disorder (HAND). HAND is associated with neurocognitive impairment, including motor impairment, and memory loss. HIV has been detected in the brain within 8 days of estimated exposure and the mechanisms for this early entry are being actively studied. Once having entered into the central nervous system (CNS), HIV degrades the blood–brain barrier through the production of its gp120 and Tat proteins. These proteins are directly toxic to endothelial cells and neurons, and propagate inflammatory cytokines by the activation of immune cells and dysregulation of tight junction proteins. The BBB breakdown is associated with the progression of neurocognitive disease. One of the main hurdles for treatment for HAND is the latent pool of cells, which are insensitive to cART and prolong inflammation by harboring the provirus in long-lived cells that can reactivate, causing damage. Multiple strategies are being studied to combat the latent pool and HAND; however, clinically, these approaches have been insufficient and require further revisions. The goal of this paper is to aggregate the known mechanisms and challenges associated with HAND. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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30. Advances in the study of polydopamine nanotechnology in central nervous system disorders.
- Author
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Sijing Ren, Xiangyu Xiao, Jiahua Lv, Shaomin Lv, Xingchen Wang, Ruihan Liu, and Qing-xia Kong
- Subjects
CENTRAL nervous system ,BLOOD-brain barrier ,PATHOLOGY ,REACTIVE oxygen species ,ALZHEIMER'S disease ,NANOTECHNOLOGY ,NANOMEDICINE - Abstract
Disorders of the central nervous system (CNS) constitute a significant global health concern at the moment. Most CNS disorders are characterized by severe neuronal damage with excessive production of reactive oxygen species, which induces high levels of oxidative stress and intense inflammatory responses in the affected tissues, thus aggravating disease pathology. Notably, the blood-brain barrier makes it difficult to deliver many drugs and biologics to the CNS, which creates great difficulties in the diagnosis and treatment of CNS disorders. Recent research on polydopamine nanotechnology has led to the discovery of many promising properties; it shows strong scavenging ability for reactive oxygen species, prevents activation of pro-inflammatory microglia, and its repair function can reduce brain damage and protect neurons. Moreover, polydopamine nanotechnology can improve the blood-brain barrier permeability of biologics and reduce their neurotoxicity. It is therefore a promising candidate in the treatment of CNS disorders associated with oxidative stress. In the present paper, we review the functionality of polydopamine nanotechnology as well as the potential and recent advances of polydopaminebased nanosystems in the diagnosis and treatment of various CNS disorders, including Alzheimer's disease, Parkinson's disease, stroke, spinal cord injury, and glioma. Finally, we predict how polydopamine nanoparticles may guide future therapeutic strategies to address CNS disorders such as epilepsy, which currently have no cure. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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- View/download PDF
31. RETRACTED: The efficacy and adverse effects of anlotinib in the treatment of high-grade glioma: A retrospective analysis.
- Author
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Fangcheng Shen, Jing Li, Feng Liu, Ni Sun, XiangNan Qiu, Wei Ding, and XiangDong Sun
- Subjects
GLIOMAS ,ANLOTINIB ,KARNOFSKY Performance Status ,RETROSPECTIVE studies ,CENTRAL nervous system ,CHEMORADIOTHERAPY ,TUMOR grading - Abstract
Introduction: Anlotinib, a novel multi-kinase inhibitor, was found to improve progression-free survival (PFS) in brain metastases. Methods: This paper retrospectively analyzed 26 newly diagnosed or recurrent high-grade gliomas from 2017 to 2022, and the patients received oral anlotinib during concurrent postoperative chemoradiotherapy or after recurrence. Efficacy was evaluated according to the Response Assessment in Neuro-Oncology (RANO) criteria, and the main study endpoints were PFS at 6 months and overall survival (OS) at 1 year. Results: After the follow-up, until May 2022, 13 patients survived and 13 patients died, with a median follow-up time of 25.6 months. The disease control rate (DCR) was 96.2% (25/26), and the overall response rate (ORR) rate was 73.1% (19/26). The median PFS after oral anlotinib was 8.9 months (0.8--15.1), and the PFS at 6 months was 72.5%. The median OS after oral anlotinib was 12 months (1.6--24.4), and the OS at 12 months was 42.6%. Anlotinib-related toxicities were observed in 11 patients, mostly grades 1--2. In the multivariate analysis, patients with Karnofsky Performance Scale (KPS) above 80 had a highermedian PFS of 9.9months (p = 0.02), and their sex, age, IDH mutation, MGMTmethylation, and whether anlotinib was combined with chemoradiotherapy or maintenance treatment had no effect on PFS. Conclusion: We found that anlotinib combined with chemoradiotherapy in treating high-grade central nervous system (CNS) tumors can prolong PFS and OS and that it was safe. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
32. Ultraflexible PEDOT:PSS/IrO x -Modified Electrodes: Applications in Behavioral Modulation and Neural Signal Recording in Mice.
- Author
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Wang, Xueying, Jiang, Wanqi, Yang, Huiran, Ye, Yifei, Zhou, Zhitao, Sun, Liuyang, Nie, Yanyan, Tao, Tiger H., and Wei, Xiaoling
- Subjects
DEEP brain stimulation ,BRAIN-computer interfaces ,ELECTRODES ,CENTRAL nervous system ,CHARGE injection ,CLINICAL neurosciences - Abstract
Recent advancements in neural probe technology have become pivotal in both neuroscience research and the clinical management of neurological disorders. State-of-the-art developments have led to the advent of multichannel, high-density bidirectional neural interfaces that are adept at both recording and modulating neuronal activity within the central nervous system. Despite this progress, extant bidirectional probes designed for simultaneous recording and stimulation are beset with limitations, including elicitation of inflammatory responses and insufficient charge injection capacity. In this paper, we delineate the design and application of an innovative ultraflexible bidirectional neural probe engineered from polyimide. This probe is distinguished by its ability to facilitate high-resolution recordings and precise stimulation control in deep brain regions. Electrodes enhanced with a PEDOT:PSS/IrO
x composite exhibit a substantial increase in charge storage capacity, escalating from 0.14 ± 0.01 mC/cm2 to an impressive 24.75 ± 0.18 mC/cm2 . This augmentation significantly bolsters the electrodes' charge transfer efficacy. In tandem, we observed a notable reduction in electrode impedance, from 3.47 ± 1.77 MΩ to a mere 41.88 ± 4.04 kΩ, while the phase angle exhibited a positive shift from −72.61 ± 1.84° to −34.17 ± 0.42°. To substantiate the electrodes' functional prowess, we conducted in vivo experiments, where the probes were surgically implanted into the bilateral motor cortex of mice. These experiments involved the synchronous recording and meticulous analysis of neural signal fluctuations during stimulation and an assessment of the probes' proficiency in modulating directional turning behaviors in the subjects. The empirical evidence corroborates that targeted stimulation within the bilateral motor cortex of mice can modulate the intensity of neural signals in the stimulated locale, enabling the directional control of the mice's turning behavior to the contralateral side of the stimulation site. [ABSTRACT FROM AUTHOR]- Published
- 2024
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- View/download PDF
33. The Canadian Breast Cancer Symposium 2023 Meeting Report.
- Author
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Cil, Tulin, Boileau, Jean-François, Chia, Stephen, DeCoteau, MJ, Jerzak, Katarzyna J., Koch, Anne, Nixon, Nancy, Quan, May Lynn, Roberts, Amanda, and Brezden-Masley, Christine
- Subjects
BREAST cancer ,MEDICAL personnel ,CENTRAL nervous system ,ONCOLOGIC surgery ,DUCTAL carcinoma ,CARCINOMA in situ ,EXPERIMENTAL medicine ,ONCOLOGY nursing - Abstract
On 15–16 June 2023, healthcare professionals and breast cancer patients and advocates from across Canada met in Toronto, Ontario, for the 2023 Canadian Breast Cancer Symposium (CBSC.). The CBSC. is a national, multidisciplinary event that occurs every 2 years with the goal of developing a personalized approach to the management of breast cancer in Canada. Experts provided state-of-the-art information to help optimally manage breast cancer patients, including etiology, prevention, diagnosis, experimental biology, and therapy of breast cancer and premalignant breast disease. The symposium also had the objectives of increasing communication and collaboration among breast cancer healthcare providers nationwide and providing a comprehensive and real-life review of the many facets of breast cancer. The sessions covered the patient voice, the top breast cancer papers from different disciplines in 2022, artificial intelligence in breast cancer, systemic therapy updates, the management of central nervous system metastases, multidisciplinary management of ductal carcinoma in situ, special populations, optimization-based individual prognostic factors, toxicity management of novel therapeutics, survivorship, and updates in surgical oncology. The key takeaways of these sessions have been summarized in this conference report. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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34. The Development of a New Patient-Reported Outcome Measure in Recessive Ataxias: The Person-Reported Ataxia Impact Scale.
- Author
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Tremblay, Marjolaine, Brais, Bernard, Asselin, Véronique, Buffet, Martin, Girard, André, Girard, Denis, Berbiche, Djamal, and Gagnon, Cynthia
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ATAXIA ,PERIPHERAL nervous system ,TEST validity ,NEUROLOGICAL disorders ,CENTRAL nervous system - Abstract
Autosomal recessive cerebellar ataxias (ARCAs) are inherited neurological disorders that can affect both the central and peripheral nervous systems. To assess the effects of interventions according to the perception of people affected, patient-reported outcome measures (PROMs) must be available. This paper presents the development process of the Person-Reported Ataxia Impact Scale (PRAIS), a new PROM in recessive ataxias, and the documentation of its content validity, interpretability, and construct validity (structural and discriminant). The development followed the PROMIS framework and the Food and Drug Administration guidelines. A mixed-method study design was used to develop the PROM. A systematic review of the literature, semistructured interviews, and discussion groups was conducted to constitute an item pool. Experts' consultation helped formulate items, and the questionnaire was sent online to be completed by people affected. Statistical analyses were performed to assess the structural and discriminant validity. A total of 125 people affected by recessive ataxia completed the questionnaire. The factor analysis confirmed the three components: physical functions and activities, mental functions, and social functions. The statistical analysis showed that it can discriminate between stages of mobility and level of autonomy. It showed very good levels of internal consistency (0.79 to 0.89). The Person-Reported Ataxia Impact Scale (PRAIS) is a 38-item questionnaire that assesses the manifestations and impacts of the disease according to the perception of people affected by recessive ataxia. It can be used in clinical and research settings. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
35. Electroacupuncture stimulation enhances the permeability of the blood-brain barrier: A systematic review and meta-analysis of preclinical evidence and possible mechanisms.
- Author
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Xu, Nuo, Gong, Peng, Xu, Shiting, Chen, Yangyun, Dai, Mengyuan, Jia, Zhaoxing, and Lin, Xianming
- Subjects
BLOOD-brain barrier ,GLIAL fibrillary acidic protein ,ELECTROACUPUNCTURE ,VASCULAR endothelial growth factors ,NERVE growth factor ,CENTRAL nervous system - Abstract
An important cellular barrier to maintain the stability of the brain's internal and external environment is the blood-brain barrier (BBB). It also prevents harmful substances from entering brain tissue through blood circulation while providing protection for the central nervous system. It should be noted, however, that the intact BBB can be a barrier to the transport of most drugs into the brain via the conventional route of administration, which can prevent them from reaching effective concentrations for the treatment of disorders affecting the central nervous system. Electroacupuncture stimulation has been shown to be effective at opening the BBB in a series of experimental studies. This study systematically analyzes the possibility and mechanism by which electroacupuncture opens the BBB. In PubMed, Web of Science, VIP Database, Wanfang Database, and the Chinese National Knowledge Infrastructure, papers have been published for nearly 22 years aimed at opening the BBB and its associated structures. A comparison of EB content between electroacupuncture and control was selected as the primary outcome. There were also results on vascular endothelial growth factor (VEGF), nerve growth factor (NGF), P-Glycoprotein (P-gp), Matrix Metalloproteinase 9 (MMP-9), and glial fibrillary acidic protein (GFAP). We utilized Review Manager software analysis to analyze correlations between studies with a view to exploring the mechanisms of similarity. Evans Blue infiltration forest plot: pooled effect size of 2.04, 95% CI: 1.21 to 2.87, P < 0.01. These results indicate that electroacupuncture significantly increases EB penetration across the BBB. Most studies have reported that GFAP, MMP-9, and VEGF were upregulated after treatment. P-gp expression decreased as well. Electroacupuncture can open the BBB, and the sparse-dense wave is currently the most effective electroacupuncture frequency for opening the BBB. VEGF plays an important role in opening the BBB. It is also important to regulate the expression of MMP-9 and GFAP and inhibit the expression of P-gp. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
36. The efficacy and adverse effects of anlotinib in the treatment of high-grade glioma: A retrospective analysis.
- Author
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Fangcheng Shen, Jing Li, Feng Liu, Ni Sun, XiangNan Qiu, Wei Ding, and XiangDong Sun
- Subjects
GLIOMAS ,ANLOTINIB ,KARNOFSKY Performance Status ,RETROSPECTIVE studies ,CENTRAL nervous system ,CHEMORADIOTHERAPY ,TUMOR grading - Abstract
Introduction: Anlotinib, a novel multi-kinase inhibitor, was found to improve progression-free survival (PFS) in brain metastases. Methods: This paper retrospectively analyzed 26 newly diagnosed or recurrent high-grade gliomas from 2017 to 2022, and the patients received oral anlotinib during concurrent postoperative chemoradiotherapy or after recurrence. Efficacy was evaluated according to the Response Assessment in Neuro-Oncology (RANO) criteria, and the main study endpoints were PFS at 6 months and overall survival (OS) at 1 year. Results: After the follow-up, until May 2022, 13 patients survived and 13 patients died, with a median follow-up time of 25.6 months. The disease control rate (DCR) was 96.2% (25/26), and the overall response rate (ORR) rate was 73.1% (19/26). The median PFS after oral anlotinib was 8.9 months (0.8-15.1), and the PFS at 6 months was 72.5%. The median OS after oral anlotinib was 12 months (1.6-24.4), and the OS at 12 months was 42.6%. Anlotinib-related toxicities were observed in 11 patients, mostly grades 1-2. In the multivariate analysis, patients with Karnofsky Performance Scale (KPS) above 80 had a highermedian PFS of 9.9months (p = 0.02), and their sex, age, IDH mutation, MGMTmethylation, and whether anlotinib was combined with chemoradiotherapy or maintenance treatment had no effect on PFS. Conclusion: We found that anlotinib combined with chemoradiotherapy in treating high-grade central nervous system (CNS) tumors can prolong PFS and OS and that it was safe. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
37. Synthesis and Characterization of ZIF-90 Nanoparticles as Potential Brain Cancer Therapy.
- Author
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Monarca, Lorenzo, Ragonese, Francesco, Sabbatini, Paola, Caglioti, Concetta, Stamegna, Matteo, Palazzetti, Federico, Sportoletti, Paolo, Costantino, Ferdinando, and Fioretti, Bernard
- Subjects
BRAIN cancer ,CANCER treatment ,NANOPARTICLES ,CENTRAL nervous system ,DRUG therapy - Abstract
Human glioblastoma is probably the most malignant and aggressive among cerebral tumors, of which it represents approximately 80% of the reported cases, with an overall survival rate that is quite low. Current therapies include surgery, chemotherapy, and radiotherapy, with associated consistent side effects and low efficacy. The hardness in reaching the site of action, and overcoming the blood–brain barrier, is a major limitation of pharmacological treatments. In this paper, we report the synthesis and characterization of ZIF-90 (ZIF, Zeolitic Imidazolate Framework) nanoparticles as putative carriers of anticancer drugs to the brain. In particular, we successfully evaluated the biocompatibility of these nanoparticles, their stability in body fluids, and their ability to uptake in U251 human glioblastoma cell lines. Furthermore, we managed to synthesize ZIF-90 particles loaded with berberine, an alkaloid reported as a possible effective adjuvant in the treatment of glioblastoma. These findings could suggest ZIF-90 as a possible new strategy for brain cancer therapy and to study the physiological processes present in the central nervous system. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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38. Navigating the Nose-to-Brain Route: A Systematic Review on Lipid-Based Nanocarriers for Central Nervous System Disorders.
- Author
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Agosti, Edoardo, Zeppieri, Marco, Antonietti, Sara, Battaglia, Luigi, Ius, Tamara, Gagliano, Caterina, Fontanella, Marco Maria, and Panciani, Pier Paolo
- Subjects
CENTRAL nervous system ,INTRANASAL administration ,NANOCARRIERS ,BLOOD-brain barrier ,ALZHEIMER'S disease ,INTRANASAL medication ,LIPIDS - Abstract
Background: The blood–brain barrier (BBB) regulates brain substance entry, posing challenges for treating brain diseases. Traditional methods face limitations, leading to the exploration of non-invasive intranasal drug delivery. This approach exploits the direct nose-to-brain connection, overcoming BBB restrictions. Intranasal delivery enhances drug bioavailability, reduces dosage, and minimizes systemic side effects. Notably, lipid nanoparticles, such as solid lipid nanoparticles and nanostructured lipid carriers, offer advantages like improved stability and controlled release. Their nanoscale size facilitates efficient drug loading, enhancing solubility and bioavailability. Tailored lipid compositions enable optimal drug release, which is crucial for chronic brain diseases. This review assesses lipid nanoparticles in treating neuro-oncological and neurodegenerative conditions, providing insights for effective nose-to-brain drug delivery. Methods: A systematic search was conducted across major medical databases (PubMed, Ovid MEDLINE, and Scopus) up to 6 January 2024. The search strategy utilized relevant Medical Subject Heading (MeSH) terms and keywords related to "lipid nanoparticles", "intranasal administration", "neuro-oncological diseases", and "neurodegenerative disorders". This review consists of studies in vitro, in vivo, or ex vivo on the intranasal administration of lipid-based nanocarriers for the treatment of brain diseases. Results: Out of the initial 891 papers identified, 26 articles met the eligibility criteria after a rigorous analysis. The exclusion of 360 articles was due to reasons such as irrelevance, non-reporting selected outcomes, the article being a systematic literature review or meta-analysis, and lack of method/results details. This systematic literature review, focusing on nose-to-brain drug delivery via lipid-based nanocarriers for neuro-oncological, neurodegenerative, and other brain diseases, encompassed 60 studies. A temporal distribution analysis indicated a peak in research interest between 2018 and 2020 (28.3%), with a steady increase over time. Regarding drug categories, Alzheimer's disease was prominent (26.7%), followed by antiblastic drugs (25.0%). Among the 65 drugs investigated, Rivastigmine, Doxorubicin, and Carmustine were the most studied (5.0%), showcasing a diverse approach to neurological disorders. Notably, solid lipid nanoparticles (SLNs) were predominant (65.0%), followed by nanostructured lipid carriers (NLCs) (28.3%), highlighting their efficacy in intranasal drug delivery. Various lipids were employed, with glyceryl monostearate being prominent (20.0%), indicating preferences in formulation. Performance assessment assays were balanced, with in vivo studies taking precedence (43.3%), emphasizing the translation of findings to complex biological systems for potential clinical applications. Conclusions: This systematic review reveals the transformative potential of intranasal lipid nanoparticles in treating brain diseases, overcoming the BBB. Positive outcomes highlight the effectiveness of SLNs and NLCs, which are promising new approaches for ailments from AD to stroke and gliomas. While celebrating progress, addressing challenges like nanoparticle toxicity is also crucial. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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- View/download PDF
39. Application of artificial intelligence in HE risk prediction modelling and research advances.
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HUANG Liangji-ang, MAO Dewen, ZHENG Jinghui, WANG Minggang, and YAO Chun
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ARTIFICIAL intelligence ,HEPATIC encephalopathy ,PREDICTION models ,CENTRAL nervous system ,BRAIN diseases - Abstract
Hepatic encephalopathy is a clinical syndrome of central nervous system dysfunction caused by liver insufficiency. It severely affects the quality of life of patients and may lead to death. Accurate prediction of the risk of developing hepatic encephalopathy is crucial for early intervention and treatment. In order to identify the risk of hepatic encephalopathy in patients in advance, many studies have been devoted to efforts to develop tools and methods to identify the risk of hepatic encephalopathy as early as possible, so as to develop preventive and early management strategies. Most conventional hepatic encephalopathy risk prediction models currently assess the probability of a patient developing hepatic encephalopathy by analysing factors such as clinical data and biochemical indicators, however, their accuracy, sensitivity and positive predictive value are not high. The application of artificial intelligence to clinical predictive modelling is a very hot and promising area, which can use large amounts of data and complex algorithms to improve the accuracy and efficiency of diagnosis and prognosis. To date, there have been few studies using AI techniques to predict hepatic encephalopathy. Therefore, this paper reviews the research progress of hepatic encephalopathy risk prediction models, and also discusses the prospect of AI application in hepatic encephalopathy risk prediction models. It also points out the challenges and future research directions of AI in HE risk prediction model research in order to promote the development and clinical application of hepatic encephalopathy risk prediction models. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
40. Photobiomodulation for Neurodegenerative Diseases: A Scoping Review.
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Shen, Qi, Guo, Haoyun, and Yan, Yihua
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NEURODEGENERATION ,PHOTOBIOMODULATION therapy ,ALZHEIMER'S disease ,PARKINSON'S disease ,CENTRAL nervous system - Abstract
Neurodegenerative diseases involve the progressive dysfunction and loss of neurons in the central nervous system and thus present a significant challenge due to the absence of effective therapies for halting or reversing their progression. Based on the characteristics of neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD), which have prolonged incubation periods and protracted courses, exploring non-invasive physical therapy methods is essential for alleviating such diseases and ensuring that patients have an improved quality of life. Photobiomodulation (PBM) uses red and infrared light for therapeutic benefits and functions by stimulating, healing, regenerating, and protecting organizations at risk of injury, degradation, or death. Over the last two decades, PBM has gained widespread recognition as a non-invasive physical therapy method, showing efficacy in pain relief, anti-inflammatory responses, and tissue regeneration. Its application has expanded into the fields of neurology and psychiatry, where extensive research has been conducted. This paper presents a review and evaluation of studies investigating PBM in neurodegenerative diseases, with a specific emphasis on recent applications in AD and PD treatment for both animal and human subjects. Molecular mechanisms related to neuron damage and cognitive impairment are scrutinized, offering valuable insights into PBM's potential as a non-invasive therapeutic strategy. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
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41. Neurosyphilis: insights into its pathogenesis, susceptibility, diagnosis, treatment, and prevention.
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Sirui Wu, Fei Ye, Yuanfang Wang, and Dongdong Li
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NEUROSYPHILIS ,CEREBROSPINAL fluid examination ,WHOLE genome sequencing ,CENTRAL nervous system ,TREPONEMA pallidum ,PENICILLIN G - Abstract
Background and aim: Invasion of the central nervous system by Treponema pallidum can occur at any stage of syphilis. In the event that T. pallidum is not cleared promptly, certain individuals may experience progression to neurosyphilis, which manifests as cognitive and behavioral abnormalities, limb paralysis, and potentially fatal outcomes. Early identification or prevention of neurosyphilis is therefore crucial. The aim of this paper is to conduct a critical and narrative review of the latest information focusing exclusively to the pathogenesis and clinical management of neurosyphilis. Methodology: To compile this review, we have conducted electronic literature searches from the PubMed database relating to neurosyphilis. Priority was given to studies published from the past 10 years (from 2013 to 2023) and other studies if they were of significant importance (from 1985 to 2012), including whole genome sequencing results, cell structure of T. pallidum, history of genotyping, and other related topics. These studies are classic or reflect a developmental process. Results: Neurosyphilis has garnered global attention, yet susceptibility to and the pathogenesis of this condition remain under investigation. Cerebrospinal fluid examination plays an important role in the diagnosis of neurosyphilis, but lacks the gold standard. Intravenous aqueous crystalline penicillin G continues to be the recommended therapeutic approach for neurosyphilis. Considering its sustained prominence, it is imperative to develop novel public health tactics in order to manage the resurgence of neurosyphilis. Conclusion: This review gives an updated narrative description of neurosyphilis with special emphasis on its pathogenesis, susceptibility, diagnosis, treatment, and prevention. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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- View/download PDF
42. Designing and Manufacturing an Affordable and Easy to Use Visual Bio Feedback Device to Fix Forward Head Posture: A Pilot Study Involving Female Students.
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Emadi Andani, Mehran, Lotfalian, Bahar, and Moshayedi, Ata Jahangir
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PSYCHOLOGICAL feedback ,ORTHOPEDIC apparatus ,PILOT projects ,POSTURE ,MOTION detectors ,CENTRAL nervous system - Abstract
Forward Head Posture (FHP) is when the head leans forward due to factors such as heavy backpacks or poor computer ergonomics. FHP can lead to neck strain and discomfort as well as potential long-term issues such as arthritis. Treatment options include specialized exercises, orthopedic devices, manual therapy, physical exercises, and visual feedback techniques, along with guidance from specialists in physical medicine and rehabilitation. In this study, a visual feedback-based approach was used to address FHP in female students. The study spanned ten days and included a visual feedback group and a control group. The results showed significant improvements in maximum head angle deviation in the visual feedback group compared to the control group; however, there was no significant change in the DFA number, indicating stability in policy control by the central nervous system. The study demonstrated that visual feedback sessions led to immediate benefits, with participants progressively acquiring skills involving the maintenance of proper head positioning. The test results indicated that the neck angle decreased to less than 15 degrees, indicating a return to a normal state. The versatility of the developed affordable and easy-to-use device and the potential for using smartphone motion sensors for similar visual feedback systems are discussed in this paper as well. The study suggests the promising potential of visual feedback in healthcare, including remote monitoring and smartphone-based solutions. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
43. Astroglial Cells: Emerging Therapeutic Targets in the Management of Traumatic Brain Injury.
- Author
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Czyżewski, Wojciech, Mazurek, Marek, Sakwa, Leon, Szymoniuk, Michał, Pham, Jennifer, Pasierb, Barbara, Litak, Jakub, Czyżewska, Ewa, Turek, Michał, Piotrowski, Bartłomiej, Torres, Kamil, and Rola, Radosław
- Subjects
BRAIN injuries ,DRUG target ,CONNEXIN 43 ,MONOCLONAL antibodies ,CENTRAL nervous system ,NEURAL stem cells ,NERVE tissue - Abstract
Traumatic Brain Injury (TBI) represents a significant health concern, necessitating advanced therapeutic interventions. This detailed review explores the critical roles of astrocytes, key cellular constituents of the central nervous system (CNS), in both the pathophysiology and possible rehabilitation of TBI. Following injury, astrocytes exhibit reactive transformations, differentiating into pro-inflammatory (A1) and neuroprotective (A2) phenotypes. This paper elucidates the interactions of astrocytes with neurons, their role in neuroinflammation, and the potential for their therapeutic exploitation. Emphasized strategies encompass the utilization of endocannabinoid and calcium signaling pathways, hormone-based treatments like 17β-estradiol, biological therapies employing anti-HBGB1 monoclonal antibodies, gene therapy targeting Connexin 43, and the innovative technique of astrocyte transplantation as a means to repair damaged neural tissues. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
44. Leptin and energy balance: exploring Leptin's role in the regulation of energy intake and energy expenditure.
- Author
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Tucker, Jessica A.L., Bornath, Derek P.D., McCarthy, Seth F., and Hazell, Tom J.
- Subjects
LEPTIN receptors ,BRAIN-derived neurotrophic factor ,LEPTIN ,GHRELIN receptors ,PEPTIDES ,AMYLIN ,CENTRAL nervous system ,GHRELIN - Abstract
Leptin is a tonic appetite-regulating hormone, which is integral for the long-term regulation of energy balance. The current evidence suggests that the typical orexigenic or anorexigenic response of many of these appetite-regulating hormones, most notably ghrelin and cholecystokinin (CCK), require leptin to function whereas glucagon-like peptide-1 (GLP-1) is required for leptin to function, and these responses are altered when leptin injection or gene therapy is administered in combination with these same hormones or respective agonists. The appetite-regulatory pathway is complex, thus peptide tyrosine tyrosine (PYY), brain-derived neurotrophic factor (BDNF), orexin-A (OXA), and amylin also maintain ties to leptin, however these are less well understood. While reviews to date have focused on the existing relationships between leptin and the various neuropeptide modulators of appetite within the central nervous system (CNS) or it's role in thermogenesis, no review paper has synthesised the information regarding the interactions between appetite-regulating hormones and how leptin as a chronic regulator of energy balance can influence the acute appetite-regulatory response. Current evidence suggests that potential relationships exist between leptin and the circulating peripheral appetite hormones ghrelin, GLP-1, CCK, OXA and amylin to exhibit either synergistic or opposing effects on appetite inhibition. Though more research is warranted, leptin appears to be integral in both energy intake and energy expenditure. More specifically, functional leptin receptors appear to play an essential role in these processes. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
45. The modulatory role of gut microbiota on host behavior: exploring the interaction between the brain-gut axis and the neuroendocrine system.
- Author
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Awe, Temitope, Fasawe, Ayoola, Sawe, Caleb, Ogunware, Adedayo, Jamiu, Abdullahi Temitope, and Allen, Michael
- Subjects
GUT microbiome ,NEUROENDOCRINE system ,MICROBIAL communities ,CENTRAL nervous system ,GASTROINTESTINAL system - Abstract
The brain-gut axis refers to the communication between the central nervous system and the gastrointestinal tract, with the gut microbiome playing a crucial role. While our understanding of the interaction between the gut microbiome and the host's physiology is still in its nascent stage, evidence suggests that the gut microbiota can indeed modulate host behavior. Understanding the specific mechanisms by which the gut microbiota community modulates the host's behavior remains the focus of present and future neuro-gastroenterology studies. This paper reviews several pieces of evidence from the literature on the impact of gut microbiota on host behavior across animal taxa. We explore the different pathways through which this modulation occurs, with the aim of deepening our understanding of the fascinating relationship between the gut microbiome and the central nervous system. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
46. The Associations of Vitamin D with Ovarian Reserve Markers and Depression: A Narrative Literature Review.
- Author
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Jeon, Gyun-Ho
- Abstract
Since the identification of vitamin D receptors in both the female reproductive tract and the central nervous system, further data have shown that vitamin D is involved in the processes of reproductive and mental health. This paper reviews current research on the associations of vitamin D with ovarian reserve markers and depression and discusses the potential role of vitamin D in their relationships. There have been numerous studies reporting that vitamin D was significantly related to ovarian reserve markers and depression in basic or clinical research, but some observational and interventional clinical studies have shown inconsistent results. Nevertheless, recent meta-analyses of interventional studies have provided promising results showing that vitamin D supplementation significantly improves ovarian reserve metrics, especially in a subgroup of women with normal or diminished ovarian reserve, and decreases depressive symptoms and risk. The demonstration of an association of vitamin D with both ovarian reserve and depression could suggest that vitamin D may be another important key in explaining female reproductive depression. Larger-scale studies in standardized settings will be needed in order to gain further insight into the role of vitamin D in female reproduction and depression. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
47. Toxicity spectrum and detrimental effects of titanium dioxide nanoparticles as an emerging pollutant: A review.
- Author
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Manzoora, Qaisar, Sajida, Arfaa, Alia, Zulfiqar, Nazir, Arif, Sajid, Anam, Imtiaz, Faiza, Iqbal, Shahid, Younas, Umer, Arif, Hamza, and Iqbal, Munawar
- Subjects
TITANIUM dioxide nanoparticles ,EMERGING contaminants ,HUMAN body ,ALIMENTARY canal ,CENTRAL nervous system ,BLOOD-brain barrier - Abstract
Titanium dioxide nanoparticles have wide industrial--applications, due to their enhanced mechanical, physical, optical and electrical properties. TiO
2 -based nanomaterials are extensively used in different industries for example paper, semiconductors, paint, food, cosmetics, water purification and textile. Besides its multiple applications in different domains of life, TiO2 has been reported for its hazardous effect on ecosystems, specifically on humans and mammals. The human body may be exposed to TiO2 NPs by three pathways i.e., oral, dermal and intra-gastric pathways and get accumulated in different parts of the body like the spleen, alimentary tract, central nervous system, liver, kidney, reproductive system, cardiac muscles and may form agglomerates with other mammalian cells. Additionally, these NPs may cross blood brain barrier and induce apoptosis in human hippocampal neurons. These NPs also show genotoxic effects that might leads towards the apoptosis and chromosomal instability. It has been observed experimentally that the cytotoxic effects of TiO2 depend on their size, shape, type and rate of consumption. This paper provides comprehensive information regarding hazardous effects reported for TiO2 NPs on living organisms (animals and humans). This information will be supportive for understanding the spectrum of toxicity associated with the NPs that will be helpful in deciding the fate of TiO2 NPs. [ABSTRACT FROM AUTHOR]- Published
- 2024
- Full Text
- View/download PDF
48. Exploring the Central Mechanisms of Botulinum Toxin in Parkinson's Disease: A Systematic Review from Animal Models to Human Evidence.
- Author
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Cutrona, Carolina, Marchet, Francesco, Costanzo, Matteo, De Bartolo, Maria Ilenia, Leodori, Giorgio, Ferrazzano, Gina, Conte, Antonella, Fabbrini, Giovanni, Berardelli, Alfredo, and Belvisi, Daniele
- Subjects
BOTULINUM A toxins ,BOTULINUM toxin ,PARKINSON'S disease ,ANIMAL models in research ,CENTRAL nervous system ,SENSORIMOTOR integration - Abstract
Botulinum toxin (BoNT) is an effective and safe therapy for the symptomatic treatment of several neurological disturbances. An important line of research has provided numerous pieces of evidence about the mechanisms of action of BoNT in the central nervous system, especially in the context of dystonia and spasticity. However, only a few studies focused on the possible central effects of BoNT in Parkinson's disease (PD). We performed a systematic review to describe and discuss the evidence from studies focused on possible central effects of BoNT in PD animal models and PD patients. To this aim, a literature search in PubMed and SCOPUS was performed in May 2023. The records were screened according to title and abstract by two independent reviewers and relevant articles were selected for full-text review. Most of the papers highlighted by our review report that the intrastriatal administration of BoNT, through local anticholinergic action and the remodulation of striatal compensatory mechanisms secondary to dopaminergic denervation, induces an improvement in motor and non-motor symptoms in the absence of neuronal loss in animal models of PD. In human subjects, the data are scarce: a single neurophysiological study in tremulous PD patients found that the change in tremor severity after peripheral BoNT administration was associated with improved sensory–motor integration and intracortical inhibition measures. Further clinical, neurophysiological, and neuroimaging studies are necessary to clarify the possible central effects of BoNT in PD. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
49. From Development to Place in Therapy of Lorlatinib for the Treatment of ALK and ROS1 Rearranged Non-Small Cell Lung Cancer (NSCLC).
- Author
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Fabbri, Laura, Di Federico, Alessandro, Astore, Martina, Marchiori, Virginia, Rejtano, Agnese, Seminerio, Renata, Gelsomino, Francesco, and De Giglio, Andrea
- Subjects
NON-small-cell lung carcinoma ,CRIZOTINIB ,CLINICAL trials ,ANAPLASTIC large-cell lymphoma ,BLOOD-brain barrier ,BRAIN diseases - Abstract
Following the results of the CROWN phase III trial, the third-generation macrocyclic ALK inhibitor lorlatinib has been introduced as a salvage option after the failure of a first-line TKI in ALK-rearranged NSCLC, while its precise role in the therapeutic algorithm of ROS1 positive disease is still to be completely defined. The ability to overcome acquired resistance to prior generation TKIs (alectinib, brigatinib, ceritinib, and crizotinib) and the high intracranial activity in brain metastatic disease thanks to increased blood–brain barrier penetration are the reasons for the growing popularity and interest in this molecule. Nevertheless, the major vulnerability of this drug resides in a peculiar profile of related collateral events, with neurological impairment being the most conflicting and debated clinical issue. The cognitive safety concern, the susceptibility to heterogeneous resistance pathways, and the absence of a valid alternative in the second line are strongly jeopardizing a potential paradigm shift in this oncogene-addicted disease. So, when prescribing lorlatinib, clinicians must face two diametrically opposed characteristics: a great therapeutic potential without the intrinsic limitations of its precursor TKIs, a cytotoxic activity threatened by suboptimal tolerability, and the unavoidable onset of resistance mechanisms we cannot properly manage yet. In this paper, we give a critical point of view on the stepwise introduction of this promising drug into clinical practice, starting from its innovative molecular and biochemical properties to intriguing future developments, without forgetting its weaknesses. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
50. Editorial: Pathway to recovery: understanding the plastic changes in neural circuits leading to recovery.
- Author
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Sahin, Mesut, Meehan, Sean K., and McConnell, George C.
- Subjects
NEURAL circuitry ,CENTRAL nervous system ,NERVOUS system ,PLASTICS ,SPINAL cord - Abstract
This article, titled "Editorial: Pathway to recovery: understanding the plastic changes in neural circuits leading to recovery," discusses the potential for the nervous system to reorganize and adapt following injury, and the challenges of harnessing this potential for functional recovery. The article presents a multidisciplinary approach to understanding how the nervous system responds to injury and how adjunctive therapies and assistive technologies can be used to promote sensorimotor recovery and improve quality of life. The article also highlights the complexity of the central nervous system's response to injury and explores the potential for non-invasive neuromodulation as a therapy. Additionally, the article discusses the feasibility of methodologies used to evaluate sensorimotor function and quantify plastic changes in the nervous system. The authors hope that the findings presented in this article will inspire cross-disciplinary collaborations and accelerate the development of new approaches and technologies for individuals affected by nervous system diseases or injuries. [Extracted from the article]
- Published
- 2024
- Full Text
- View/download PDF
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