Treatment Of Nervous System Diseases Research Articles

Human cytomegalovirus infection impairs neural differentiation via repressing sterol regulatory element binding protein 2-mediated cholesterol biosynthesis

Congenital human cytomegalovirus (HCMV) infection is a major cause of abnormalities and disorders in the central nervous system (CNS) and/or the peripheral nervous system (PNS). However, the complete pathogenesis of neural differentiation disorders caused by HCMV infection remains to be fully elucidated. Stem cells from human exfoliated deciduous teeth (SHEDs) are mesenchymal stem cells (MSCs) with a high proliferation and neurogenic differentiation capacity. Since SHEDs originate from the neural crest of the early embryonic ectoderm, SHEDs were hypothesized to serve as a promising cell line for investigating the pathogenesis of neural differentiation disorders in the PNS caused by congenital HCMV infection. In this work, SHEDs were demonstrated to be fully permissive to HCMV infection and the virus was able to complete its life cycle in SHEDs. Under neurogenic inductive conditions, HCMV infection of SHEDs caused an abnormal neural morphology. The expression of stem/neural cell markers was also disturbed by HCMV infection. The impairment of neural differentiation was mainly due to a reduction of intracellular cholesterol levels caused by HCMV infection. Sterol regulatory element binding protein-2 (SREBP2) is a critical transcription regulator that guides cholesterol synthesis. HCMV infection was shown to hinder the migration of SREBP2 into nucleus and resulted in perinuclear aggregations of SREBP2 during neural differentiation. Our findings provide new insights into the prevention and treatment of nervous system diseases caused by congenital HCMV infection.

Advances in the application of fecal microbiota transplantation for the treatment of nervous system diseases

The intestinal microbiota exhibits a strong correlation with the function of the central nervous system, exerting influence on the host brain through neural pathways, immune pathways, and microbial metabolites along the gut-brain axis. Disorders in the composition of the intestinal microbial are closely associated with the onset and progression of neurological disorders, such as depression, Alzheimer's disease, and Parkinson's disease. It has been proven that fecal microbiota transplantation can improve symptoms in animal models of neurological diseases and clinical patients. This paper provides a comprehensive review of the composition and function of the human intestinal microbiota, as well as the intricate the relationship between the human intestinal microbiota and nervous system diseases through the gut-brain axis. Additionally, it delves into the research advancements and underlying mechanism of fecal microbiota transplantation in the treatment of nervous system diseases. These findings offer novel insights and potential avenues for clinical interventions targeting nervous system diseases.

Research progress on mechanisms of ligustilide in treatment of nervous system diseases

Ligustilide is the main active component of the volatile oil from Angelica sinensis and Ligusticum chuanxiong in the Umbelliferae family. It is a phthalein compound with anti-inflammatory, analgesic, antioxidant, anti-tumor, anti-atherosclerosis, neuroprotective, and other pharmacological effects. It can improve the permeability of the blood-brain barrier and has important potential in the treatment of neurodegenerative diseases and other nervous system diseases, such as Alzheimer's disease, ischemic stroke, Parkinson's disease, vascular dementia, and depression. Therefore, the mechanism of ligustilide in the treatment of nervous system diseases was summarized to provide a reference for drug development and clinical application.

Treatment of Syringomyelia Characterized by Focal Dilatation of the Central Canal Using Mesenchymal Stem Cells and Neural Stem Cells.

Syringomyelia is a progressive chronic disease that leads to nerve pain, sensory dissociation, and dyskinesia. Symptoms often do not improve after surgery. Stem cells have been widely explored for the treatment of nervous system diseases due to their immunoregulatory and neural replacement abilities. In this study, we used a rat model of syringomyelia characterized by focal dilatation of the central canal to explore an effective transplantation scheme and evaluate the effect of mesenchymal stem cells and induced neural stem cells for the treatment of syringomyelia. The results showed that cell transplantation could not only promote syrinx shrinkage but also stimulate the proliferation of ependymal cells, and the effect of this result was related to the transplantation location. These reactions appeared only when the cells were transplanted into the cavity. Additionally, we discovered that cell transplantation transformed activated microglia into the M2 phenotype. IGF1-expressing M2 microglia may play a significant role in the repair of nerve pain. Cell transplantation can promote cavity shrinkage and regulate the local inflammatory environment. Moreover, the proliferation of ependymal cells may indicate the activation of endogenous stem cells, which is important for the regeneration and repair of spinal cord injury.

Research Progress of Tongqihuoxue Decoction in the Treatment of Nervous System Diseases

Research Progress of Tongqihuoxue Decoction in the Treatment of Nervous System Diseases

Coexisting discharge and synchronization of heterogeneous discrete neural network with crosstalk memristor synapses

Synaptic crosstalk, which occurs due to the overflow of neurotransmitters between neighboring synapses, holds a crucial position in shaping the discharge characteristics and signal transmission within nervous systems. In this paper, two memristors are employed to simulate biological neural synapses and bidirectionally couple Chialvo discrete neuron and Rulkov discrete neuron. Thus, a heterogeneous discrete neural network with memristor-synapse coupling is constructed that takes into account the crosstalk behavior between memristor synapses in the coupled state. The analysis demonstrates that the quantity and stability of fixed points within this neural network intimately depend on the strength of synaptic crosstalk. Additionally, through a thorough investigation of bifurcation diagrams, phase diagrams, Lyapunov exponents, and time sequences, we uncover the multi-stable state property exhibited by the neural network. This property manifests in the coexistence of diverse discharge behaviors, which vary significantly with the synaptic crosstalk strength. Intriguingly, the introduction of control parameter to state variable triggers offset boosting and the emergence of infinite stable states within the neural network. Furthermore, we conducted a comprehensive study to explore the influence of synaptic crosstalk strength on the synchronization behavior of the neural network, considering various coupling strengths, initial conditions, and parameters. Our analysis, which was founded on the phase difference and synchronization factor of neuronal discharge sequences, revealed that the neural network maintains phase synchronization despite the variations of the two crosstalk strengths. The insights gained from this paper provide significant support in elucidating the electrophysiological mechanisms underlying biological neural information processing and transmission. Especially, the coexisting discharge phenomenon in the neural network provides an electrophysiological theoretical foundation for the clinical symptoms and diagnosis of the same neurological disease among different individuals or at different stages. And the doctors can predict the progression and prognosis of neurological disease based on the patterns and characteristics of coexisting discharge in patients, enabling them to adopt appropriate intervention measures and monitoring plans. Therefore, the research on coexisting discharge in the neural system contributes to the comprehensive treatment of nervous system disease.

Potential therapeutic effect of olfactory ensheathing cells in neurological diseases: neurodegenerative diseases and peripheral nerve injuries.

Neurological diseases are destructive, mainly characterized by the failure of endogenous repair, the inability to recover tissue damage, resulting in the increasing loss of cognitive and physical function. Although some clinical drugs can alleviate the progression of these diseases, but they lack therapeutic effect in repairing tissue injury and rebuilding neurological function. More and more studies have shown that cell therapy has made good achievements in the application of nerve injury. Olfactory ensheathing cells (OECs) are a special type of glial cells, which have been proved to play an important role as an alternative therapy for neurological diseases, opening up a new way for the treatment of neurological problems. The functional mechanisms of OECs in the treatment of neurological diseases include neuroprotection, immune regulation, axon regeneration, improvement of nerve injury microenvironment and myelin regeneration, which also include secreted bioactive factors. Therefore, it is of great significance to better understand the mechanism of OECs promoting functional improvement, and to recognize the implementation of these treatments and the effective simulation of nerve injury disorders. In this review, we discuss the function of OECs and their application value in the treatment of neurological diseases, and position OECs as a potential candidate strategy for the treatment of nervous system diseases.

Comprehensive review on sexual dimorphism to improve scalp acupuncture in nervous system disease.

With the development of modern medicine, the Traditional Chinese Medicine (TCM) combined with western medicine began to be produced and applied. Scalp acupuncture (SA) as a Chinese medicine based on neurological theory, has a great advantage compared with TCM in the treatment of nervous system diseases. In this paper, we analyze the physiological and pathological manifestations of sexual dimorphism (SD) to illustrate the necessity of SD treatment. In addition, we review the factors that can affect SD and analyze in physiological structure, function, and pathological neurons. Diseases (pathological basis, pathological manifestations, and incidence) and factors leading to gender differences, which to analyze the possibility of gender differences in SA. Furthermore, we creatively a new insight of SD-SA and provide the complete SD treatment cases on the basis of the existing SA in different kinds of diseases including stroke, migraine, attention deficit hyperactivity disorder (ADHD), and depression. In summary, we believe that it is feasible to improve the clinical effectiveness of SA, which is able to promote the development of SA, and then provides an actionable evidence for the promotion of precision medicine in the future.

Research on the Effects of Neuroglobin on Ferroptosis in the Nerve Cells

Abstract Objectives The objective of this article was to explore the effects of neuroglobin (NGB) on ferroptosis in the nerve cells. Methods The NGB knockdown model of HT22 cells was constructed, and the ferroptosis-related indexes of cell proliferation activity, contents of iron ion, malondialdehyde (MDA), superoxide and reactive oxygen, and the changes of nuclear factor E2-related factor 2 (Nrf2) expression were examined in the normal group, erastin group, NGB siRNA group, and NGB siRNA + Erastin group, respectively. Results Compared with the normal group, cell proliferation activity and Nrf2 expression were significantly lower in the erastin group, NGB siRNA group, and NGB siRNA + erastin group, and ferroptosis-related indexes such as iron ion content, MDA content, superoxide content, and reactive oxygen species content were significantly reduced, and the difference between NGB siRNA + erastin group, erastin group, and NGB siRNA group was statistically significant (p < 0.05). Conclusion Knockdown of NGB in cells enhances the action of the ferroptosis inducer erastin, and NGB may regulate the cellular ferroptosis process through Nrf2. This research may provide references for the clinical treatment of nervous system disease with Chinese medicine.

Design, synthesis, and evaluation of N-methyl-propargylamine derivates as isoform-selective monoamine oxidases inhibitors for the treatment of nervous system diseases

A novel series of N-methyl-propargylamine derivates were designed, synthesized, and evaluated as isoform-selective monoamine oxidases (MAO) inhibitors for the treatment of nervous system diseases. The in vitro studies showed some of the compounds exhibited considerable MAO-A selective inhibitory activity (IC50 of 14.86–17.16 nM), while some of the others exhibited great MAO-B selective inhibitory activity (IC50 of 4.37–17.00 nM). Further studies revealed that compounds A2 （IC50 against MAO-A: 17.16 ± 1.17 nM） and A5 (IC50 against MAO-B: 17.00 ± 1.10 nM) had significant abilities to protect PC12 cells from H2O2-induced apoptosis and reactive oxygen species (ROS) production. The parallel artificial membrane permeability assay showed A2 and A5 would be potent to cross the blood–brain barrier. The results indicated that A2 showed potential use in the therapy of MAO-A related diseases, such as depression and anxiety; while A5 exhibited promising ability in the treatment of MAO-B related diseases, such as Alzheimer’s disease and Parkinson’s disease.

CDBA: a novel multi-branch feature fusion model for EEG-based emotion recognition.

EEG-based emotion recognition through artificial intelligence is one of the major areas of biomedical and machine learning, which plays a key role in understanding brain activity and developing decision-making systems. However, the traditional EEG-based emotion recognition is a single feature input mode, which cannot obtain multiple feature information, and cannot meet the requirements of intelligent and high real-time brain computer interface. And because the EEG signal is nonlinear, the traditional methods of time domain or frequency domain are not suitable. In this paper, a CNN-DSC-Bi-LSTM-Attention (CDBA) model based on EEG signals for automatic emotion recognition is presented, which contains three feature-extracted channels. The normalized EEG signals are used as an input, the feature of which is extracted by multi-branching and then concatenated, and each channel feature weight is assigned through the attention mechanism layer. Finally, Softmax was used to classify EEG signals. To evaluate the performance of the proposed CDBA model, experiments were performed on SEED and DREAMER datasets, separately. The validation experimental results show that the proposed CDBA model is effective in classifying EEG emotions. For triple-category (positive, neutral and negative) and four-category (happiness, sadness, fear and neutrality), the classification accuracies were respectively 99.44% and 99.99% on SEED datasets. For five classification (Valence 1-Valence 5) on DREAMER datasets, the accuracy is 84.49%. To further verify and evaluate the model accuracy and credibility, the multi-classification experiments based on ten-fold cross-validation were conducted, the elevation indexes of which are all higher than other models. The results show that the multi-branch feature fusion deep learning model based on attention mechanism has strong fitting and generalization ability and can solve nonlinear modeling problems, so it is an effective emotion recognition method. Therefore, it is helpful to the diagnosis and treatment of nervous system diseases, and it is expected to be applied to emotion-based brain computer interface systems.

Advances of Research on Auricular Vagus Nerve Stimulation for Treatment of Nervous System Diseases

As a new type of nerve regulation technology, Vagus Nerve Stimulation is currently used in the treatment of nervous system diseases. Auricular Vagus Nerve Stimulation has become one of the research hotspots in this field, because there is no implantation risk. However, there is no unified standard for the treatment parameters of aVNS for nervous system diseases. In this paper, the research progress of the anatomical structure and parameters of the vagus nerve and its role in nervous system diseases are reviewed to provide basis for further research.

Signal generation and regulation of implantable nerve stimulator

In the treatment of nervous system diseases, implantable nerve stimulators have attracted more and more attention because of their obvious therapeutic efficacy and high safety. The generation and regulation of stimulus signals are the most important step in the design of an implantable nerve stimulator. The stimulation signals from the implanted nerve stimulator act directly on nerve cells. If the stimulus signal is not delivered accurately according to the set parameters, it will not only affect the therapeutic effect but also cause unpredictable malignant consequences. To generate stimulus signals that meet certain requirements, the different circuit structures need to be designed to be applied to the stimulators with different function types. In this paper, five types of stimulator circuits are introduced, and their strengths and weaknesses are analyzed based on the detailed introduction of the working principles of the different stimulator circuits, which might provide a theoretical and practical reference for future research.

Apelin/APJ system: an emerging therapeutic target for neurological diseases.

Apelin, an endogenous ligand for the G protein-coupled receptor APJ, is extensively expressed in various systems, especially the nervous system. This article reviews the role of apelin/APJ system in neurological diseases. In detail, apelin/APJ system can relieve acute brain injury including subarachnoid hemorrhage, traumatic brain injury, and ischemic stroke. Also, apelin/APJ system has therapeutic effects on chronic neurodegenerative disease models, involving the regulation of neurotrophic factors, neuroendocrine, oxidative stress, neuroinflammation, neuronal apoptosis, and autophagy. In addition, through different routes of administration, apelin/APJ system has a biphasic effect on depression, epilepsy, and pain. However, apelin/APJ system exacerbates the proliferation and invasion of glioblastoma. Thus, apelin/APJ system is expected to be a therapeutic target for the treatment of nervous system diseases.

Highly adhesive stretchable polymer and highly dynamic stable human electrophysiological monitoring

<p indent="0mm">Highly dynamic and stable human electrophysiological monitoring has broad application prospects in intelligent wearable health monitoring, clinical diagnosis of cardiovascular diseases, treatment of nervous system diseases and intelligent human–computer interaction. As a signal interaction bridge between human and the external environment, on-skin electrodes can be attached to the skin surface to monitor and collect various electrophysiological signals in a non-invasive way, making it an ideal platform for highly dynamic and stable electrophysiological monitoring. From the material point of view, the highly dynamic stability of on-skin electrodes depends on the high adhesion and stretchability of the substrate. Therefore, it is an important research direction in the field of flexible intelligent health monitoring to prepare highly adhesive stretchable polymer and construct highly conformal on-skin electrodes that adhere to human skin surface through rational design of polymer structure, so as to realize highly dynamic and stable human electrophysiological monitoring. In this paper, we summarized the recent research progress in our group on the preparation of highly adhesive stretchable polymer and their applications in electrophysiological monitoring with highly dynamic stability, and discussed the opportunities and challenges of highly adhesive stretchable polymer in the next generation of flexible intelligent health monitoring.

Combination of panax ginseng and ginkgo biloba extracts attenuate cerebral ischemia injury with modulation of NLRP3 inflammasome and CAMK4/CREB pathway.

Stroke is a major cause of death and disability throughout the world. A combination of Panax Ginseng and Ginkgo biloba extracts (CGGE) is an effective treatment for nervous system diseases, but the neuroprotective mechanism underlying CGGE remains unclear. Both network analysis and experimental research were employed to explore the potential mechanism of CGGE in treating ischemic stroke (IS). Network analysis identified a total number of 133 potential targets for 34 active ingredients and 239 IS-related targets. What’s more, several processes that might involve the regulation of CGGE against IS were identified, including long-term potentiation, cAMP signaling pathway, neurotrophin signaling pathway, and Nod-like receptor signaling pathway. Our studies in animal models suggested that CGGE could reduce inflammatory response by inhibiting the activity of Nod-like receptor, pyrin containing 3 (NLRP3) inflammasome, and maintain the balance of glutamate (Glu)/gamma-aminobutyric acid (GABA) via activating calmodulin-dependent protein kinase type Ⅳ (CAMK4)/cyclic AMP-responsive element-binding protein (CREB) pathway. These findings indicated the neuroprotective effects of CGGE, possibly improving neuroinflammation and excitotoxicity by regulating the NLRP3 inflammasome and CAMK4/CREB pathway.

Integrated LC-MS/MS method and network pharmacology for exploring the characterization and mechanism of neuroprotective effect of Vitis amurensis Rupr. wine polyphenol.

Polyphenols are the main active components in Vitis amurensis Rupr. wine, which show good protective effects on the nervous system, but their compositions in Vitis amurensis Rupr. wine and the molecular mechanism underlying their neuroprotection remains unclear. The purpose of this study is to investigate the potential mechanism of the neuroprotective effect of Vitis amurensis Rupr. wine polyphenols on the basis of the specific composition of polyphenols in Vitis amurensis Rupr. wine. In this study, 40 phenolic compounds which include 15 anthocyanins, 10 flavonoids, 10 phenolic acids, 3 proanthocyanidins and 2 resveratrols were identified by UPLC Q-Exactive Orbitrap MS. Furthermore, An UPLC-QqQ/MS method was established to simultaneously determine the phenolic compounds in Vitis amurensis Rupr. Wine, and analyze the content differences of phenolic compounds between Vitis amurensis Rupr. and Vitis vinifera wine. Finally, network pharmacology was employed for the first time to predict the possible pharmacological mechanisms of Vitis amurensis wine polyphenols against nervous damage. Multivariate network analysis indicated that quercetin, (-)-epigallocatechin and various anthocyanins were found as prominent compounds for the treatment of nervous system diseases. Vitis amurensis Rupr. wine polyphenols mainly acted on these key targets, including AKT1, EGFR, ESR1, and SRC, and further regulate the PI3K-AKT and Rap1 signaling pathway for treating nervous system diseases. Our findings suggested that polyphenols in Vitis amurensis Rupr. wine possess neuroprotective effect through multicomponent, multitarget, and multichannel. PRACTICAL APPLICATIONS: Studies have revealed that Vitis amurensis Rupr. has higher levels of phenolic compounds than Vitis vinifera wine. However, due to the few and limited study of Vitis amurensis Rupr., their compositions in Vitis amurensis Rupr. wine and the molecular mechanism underlying their neuroprotection remains unclear. This research uses a holistic network pharmacology strategy to investigate the potential targets and pharmacological mechanisms of Vitis amurensis Rupr. wine polyphenols against nervous damage. To some things up, The finding elucidates the relationships between signaling pathways, targets, and compounds in Vitis amurensis Rupr. wine polyphenols, which may provide guidance and foundations for further application of medicinal food.

Thermosensitive Hydrogels and Advances in Their Application in Disease Therapy

Thermosensitive hydrogels, having unique sol–gel transition properties, have recently received special research attention. These hydrogels exhibit a phase transition near body temperature. This feature is the key to their applications in human medicine. In addition, hydrogels can quickly gel at the application site with simple temperature stimulation and without additional organic solvents, cross-linking agents, or external equipment, and the loaded drugs can be retained locally to improve the local drug concentration and avoid unexpected toxicity or side effects caused by systemic administration. All of these features have led to thermosensitive hydrogels being some of the most promising and practical drug delivery systems. In this paper, we review thermosensitive hydrogel materials with biomedical application potential, including natural and synthetic materials. We describe their structural characteristics and gelation mechanism and briefly summarize the mechanism of drug release from thermosensitive hydrogels. Our focus in this review was to summarize the application of thermosensitive hydrogels in disease treatment, including the postoperative recurrence of tumors, the delivery of vaccines, the prevention of postoperative adhesions, the treatment of nervous system diseases via nasal brain targeting, wound healing, and osteoarthritis treatment.

Effects of ginsenoside Rg1 on proliferation and directed differentiation of human umbilical cord mesenchymal stem cells into neural stem cells.

ObjectiveHuman umbilical cord mesenchymal stem cells (hUCMSCs) can be transformed into neural stem cells (NSCs) and still maintain immunomodulatory and antioxidant effects. Transplantation of NSCs induced by hUCMSCs would be a promising therapeutic strategy for the treatment of neurological diseases. Ginsenoside Rg1 has neuroprotective effects and influences cell proliferation and differentiation. In this study, we further evaluated the effects of ginsenoside Rg1 on the proliferation and directional differentiation of hUCMSCs into NSCs.MethodsThe CCK-8 assay was used to determine the optimal dose of ginsenoside Rg1 with respect to hUCMSC proliferation and differentiation. NSCs were authenticated using immunofluorescence staining and flow cytometry and were quantified in each group. RT-PCR was used to screen the signaling pathway by which ginsenoside Rg1 promoted the differentiation of hUCMSCs into NSCs.ResultsThe optimal dose of Rg1 to promote hUCMSC proliferation and differentiation to NSCs was 10 μmol/l. Flow cytometry and immunofluorescence showed that induced NSCs expressed nestin and sex-determining region Y-box 2, with higher expression levels in the Rg1 group than that in the negative control group. RT-PCR showed that Rg1 downregulates the expression of genes involved in Wnt/β-catenin and Notch signaling pathways in the induction process.ConclusionGinsenoside Rg1 not only promotes the proliferation and viability of hUCMSCs in the process of differentiation into NSCs but also improves the differentiation efficiency. This study provides a basis for the development of hUCMSC-derived NSCs for the treatment of nervous system diseases and for analyses of underlying biological mechanisms.

Gangliosides play important roles in the nervous system by regulating ion concentrations.

Gangliosides are important components of the neuronal cell membrane and play a vital role in the development of neurons and the brain. They participate in neurotransmission and are considered as the structural basis of learning and memory. Gangliosides participate in several and important physiological processes, such as cell differentiation, cell signaling, neuroprotection, nerve regeneration and apoptosis. The stability of ion concentration in excitable cells is particularly important in the maintenance of a steady state of cells and in the regulation of physiological functions. Ion concentration has been found to be related to the ganglioside's regulation in many neurological diseases, and several studies have found that they can stabilize intracellular ion concentration by regulating ion channels, which highlights their important regulatory role in neuronal excitability and synaptic transmission. Gangliosides can influence some forms of ion transport, by directly binding to ion transporters or through indirect binding and activation of transport proteins via appropriate signaling pathways. Therefore, the important and special role of gangliosides in the homeostasis of ion concentration is becoming a hot topic in the field and a theoretical basis in promoting help gangliosides use as key drugs for the treatment of nervous system diseases.