Treatment Of Nervous System Diseases Research Articles

Research progress on traditional Chinese medicine in preventing and treating cerebral ischemia injury based on "nose-brain" pathway

Due to the increasing incidence of central nervous system diseases,especially the increasing incidence and mortality of stroke,brain-targeted drug delivery has attached more and more attention. Nasal administration,as one of the ways of brain-targeted administration,can effectively make the drug delivered to the brain in a targeted way after by passing the blood-brain barrier,providing a new idea for the treatment of central nervous system diseases. Therefore,it is a promising administration way. In recent years,the treatment of encephalopathy by nasal administration of traditional Chinese medicine has become a hot topic in the research of traditional Chinese medicine. Ischemic stroke is one of the most important diseases endangering human health. Nasal administration has a history of thousands of years in treatment of stroke. Modern medical research has proved that there is a subtle connection between the nasal cavity and the brain,and the complex and ingenious structure of the nasal cavity provides the possibility for drugs delivery to the brain through the nose. Drug administration through nasal cavity has obvious advantages in treatment of central nervous system diseases represented by ischemic stroke. Nasal administration is characterized by non-invasion,low infection,rapid absorption and brain targeting. The author will expound the theoretical basis of brain targeting of nasal administration from the aspects of anatomy and physiology,and summarize the transport pathway of drugs through the nose into the brain,the in vitro and in vivo experimental research basis of the " nose-brain"pathway,and the clinical nasal administration of traditional Chinese medicine to prevent cerebral ischemia. It provides a reference for better research of drugs to prevent and treat cerebral ischemia injury through the " nose-brain"pathway and lays a foundation for further research of the " nose-brain" pathway.

The Emerging Role of Biomarkers in Adaptive Modulation of Clinical Brain Stimulation.

Therapeutic brain stimulation has proven efficacious for treatment of nervous system diseases, exerting widespread influence via disease-specific neural networks. Activation or suppression of neural networks could theoretically be assessed by either clinical symptom modification (ie, tremor, rigidity, seizures) or development of specific biomarkers linked to treatment of symptomatic disease states. For example, biomarkers indicative of disease state could aid improved intraoperative localization of electrode position, optimize device efficacy or efficiency through dynamic control, and eventually serve to guide automatic adjustment of stimulation settings. Biomarkers to control either extracranial or intracranial stimulation span from continuous physiological brain activity, intermittent pathological activity, and triggered local phenomena or potentials, to wearable devices, blood flow, biochemical or cardiac signals, temperature perturbations, optical or magnetic resonance imaging changes, or optogenetic signals. The goal of this review is to update new approaches to implement control of stimulation through relevant biomarkers. Critical questions include whether adaptive systems adjusted through biomarkers can optimize efficiency and eventually efficacy, serve as inputs for stimulation adjustment, and consequently broaden our fundamental understanding of abnormal neural networks in pathologic states. Neurosurgeons are at the forefront of translating and developing biomarkers embedded within improved brain stimulation systems. Thus, criteria for developing and validating biomarkers for clinical use are important for the adaptation of device approaches into clinical practice.

Gastrodin, a traditional Chinese medicine monomer compound, can be used as adjuvant to enhance the immunogenicity of melanoma vaccines

Gastrodin (GAS) is a Chinese medicine with wide application for the treatment of nervous system disease. Previous studies reported that GAS exhibited non-specific immunomodulatory activities. To explore the effects of GAS as a vaccine adjuvant, the expression levels of CD80, CD86, MHCI and MHCII activated markers were detected after GAS treatment in vitro and in vivo, and the expression levels of IL-2 and TNF-α in splenocytes were detected after GAS treatment in vivo. Besides, the expression levels of IL-2 and IFN-γ in CD4+T cells and perforin, TNF-α and IFN-γ in CD8+T cells were detected. The effects of GAS on the survival rate and tumor size of tumor-challenged mice and the effect of cytotoxicity on CD8+T cells were also investigated. Our data showed that GAS ameliorated CD8+T cell mediated immune response and significantly improved protection of tumor-challenged animals. The results demonstrated that GAS is a potential adjuvant contributing to anticancer immunomodulation.

MicroRNAs and nervous system diseases: network insights and computational challenges.

The nervous system is one of the most complex biological systems, and nervous system disease (NSD) is a major cause of disability and mortality. Extensive evidence indicates that numerous dysregulated microRNAs (miRNAs) are involved in a broad spectrum of NSDs. A comprehensive review of miRNA-mediated regulatory will facilitate our understanding of miRNA dysregulation mechanisms in NSDs. In this work, we summarized currently available databases on miRNAs and NSDs, star NSD miRNAs, NSD spectrum width, miRNA spectrum width and the distribution of miRNAs in NSD sub-categories by reviewing approximately 1000 studies. In addition, we characterized miRNA-miRNA and NSD-NSD interactions from a network perspective based on miRNA-NSD benchmarking data sets. Furthermore, we summarized the regulatory principles of miRNAs in NSDs, including miRNA synergistic regulation in NSDs, miRNA modules and NSD modules. We also discussed computational challenges for identifying novel miRNAs in NSDs. Elucidating the roles of miRNAs in NSDs from a network perspective would not only improve our understanding of the precise mechanism underlying these complex diseases, but also provide novel insight into the development, diagnosis and treatment of NSDs.

Panax ginseng components and the pathogenesis of Alzheimer's disease (Review).

Ginseng is one of the main representatives of traditional Chinese medicine and presents a wide range of pharmacological actions. Ginsenosides are the main class of active compounds found in ginseng. They demonstrate unique biological activity and medicinal value, namely anti-tumour, anti-inflammatory and antioxidant properties, as well as anti-apoptotic properties. Increasing levels of stress in life are responsible for the increased incidence of nervous system diseases. Neurological diseases create a huge burden on the lives and health of individuals. In recent years, studies have indicated that ginsenosides play a pronounced positive role in the prevention and treatment of neurological diseases. Nevertheless, research is still at an early stage of development, and the complex mechanisms of action involved remain largely unknown. This review aimed to shed light into what is currently known about the mechanisms of action of ginsenosides in relation to Alzheimer's disease. Scientific material and theoretical bases for the treatment of nervous system diseases with purified Panax ginseng extracts are also discussed.

Melissa officinalisand rosmarinic acid in management of memory functions and Alzheimer disease

Alzheimer disease (AD) as worldwide progressive neurodegenerative disease is prevalent disease among elderly population. Due to limitation in chemical drugs along with their adverse effects of these treatments, research for finding more effective natural drugs, is one of interesting subjects among the scientists. Melissa officinalis (M. officinalis) has a long history of use in treatment of nervous system diseases. This review article evaluates the potency of M. officinalis in treatment of AD by review of experimental and clinical documents on the efficacy, safety and its mechanisms of action in management of AD. The information is extracted from electronic resources (PubMed, Wiley, Springer and Science Direct), English and Persian scientific books. In spite of different scientific and non-scientific reports on the use of M. officinalis and its main component of rosmarinic acid in neurodegenerative diseases, there is only one clinical trial on the efficacy of M. officinalis ethanol extract in management of AD. Different mechanisms of action for M. officinalis, including inhibitory effects against amyloid beta, reactive oxygen species, and acetylcholine esterase, are involved. Larger clinical trials are recommended to confirm the efficacy and safety of M. officinalis extracts in treatment of AD patients.

Brain Iron Metabolism and CNS Diseases.

Iron is the most abundant trace element in the human body. It is well known that iron is an important component of hemoglobin involved in the transport of oxygen. As a component of various enzymes, it participates in the tricarboxylic acid cycle and oxidative phosphorylation. Iron in the nervous system is also involved in the metabolism of catecholamine neurotransmitters and is involved in the formation of myelin. Therefore, iron metabolism needs to be strictly regulated. Previous studies have shown that iron deficiency in the brain during infants and young children causes mental retardation, such as delayed development of language and body balance, and psychomotor disorders. However, if the iron is excessively deposited in the aged brain, it is closely related to the occurrence of various neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and Friedreich's ataxia. Therefore, it is important to fully study and understand the mechanism of brain iron metabolism and its regulation. On this basis, exploring the relationship between brain iron regulation and the occurrence of nervous system diseases and discovering new therapeutic targets related to iron metabolism have important significance for breaking through the limitation of prevention and treatment of nervous system diseases. This review discusses the complete research history of iron and its significant role in the pathogenesis of the central nervous system (CNS) diseases.

Postnatal neural crest stem cells from hair follicle interact with nerve tissue in vitro and in vivo.

Neural crest stem cells that located in the postnatal hair follicle (HF-NCSC) are considered a promising tool for treatment of nervous system diseases and injuries. It is well known that HF-NCSC can be used in the spinal cord and sciatic nerve reparation but their ability to restore brain structures is poorly studied. In this article we are investigating the interaction between HF-NCSC and a nerve tissue (embryonic and adult). We have found out that HF-NCSC isolated from adult mice grow and differentiate in accordance with the mouse embryo developmental stage when co-cultured with the embryonic nerve tissue. The HF-NCSC migration is slower in the late embryonic tissue co-culture system compared to the early one. This phenomenon is related to the motor function of the cells but not to their proliferation level. We have demonstrated that the embryonic nerve tissue maintains HF-NCSC an undifferentiated status, while an adult brain tissue inhibits the cell proliferation and activates the differentiation processes. Besides, HF-NCSC pre-differentiated into the neuronal direction shows a higher survival and migration rate after the transplantation into the adult brain tissue compared to the undifferentiated HF-NCSC. Thus, we have investigated the postnatal HF-NCSC response to the nerve tissue microenvironment to analyze their possible application to the brain repair processes.

Panax Notoginseng Saponins: A Review of Its Mechanisms of Antidepressant or Anxiolytic Effects and Network Analysis on Phytochemistry and Pharmacology.

Panax notoginseng (Burk) F. H. Chen, as traditional Chinese medicine, has a long history of high clinical value, such as anti-inflammatory, anti-oxidation, inhibition of platelet aggregation, regulation of blood glucose and blood pressure, inhibition of neuronal apoptosis, and neuronal protection, and its main ingredients are Panax notoginseng saponins (PNS). Currently, Panax notoginseng (Burk) F. H. Chen may improve mental function, have anti-insomnia and anti-depression effects, alleviate anxiety, and decrease neural network excitation. However, the underlying effects and the mechanisms of Panax notoginseng (Burk) F. H. Chen and its containing chemical constituents (PNS) on these depression-related or anxiety-related diseases has not been completely established. This review summarized the antidepressant or anxiolytic effects and mechanisms of PNS and analyzed network targets of antidepressant or anxiolytic actions with network pharmacology tools to provide directions and references for further pharmacological studies and new ideas for clinical treatment of nervous system diseases and drug studies and development. The review showed PNS and its components may exert these effects through regulating neurotransmitter mechanism (5-HT, DA, NE), modulation of the gamma-amino butyric acid (GABA) neurotransmission, glutamatergic system, hypo-thalamus-pituitary-adrenal (HPA) axis, brain-derived neurotrophic factor (BDNF), and its intracellular signaling pathways in the central nervous system; and produce neuronal protection by anti-inflammatory, anti-oxidation, or inhibition of neuronal apoptosis, or platelet aggregation and its intracellular signaling pathways. Network target analysis indicated PNS and its components also may have anti-inflammatory and anti-apoptotic effects, which leads to the preservation of brain nerves, and regulate the activity and secretion of nerve cells, exerting anti-depression and anxiolytic effects, which may provide new directions for further in-depth researches of related mechanisms.

Stem cells: a promising candidate to treat neurological disorders.

Neurologic impairments are usually irreversible as a result of limited regeneration in the central nervous system. Therefore, based on the regenerative capacity of stem cells, transplantation therapies of various stem cells have been tested in basic research and preclinical trials, and some have shown great prospects. This manuscript overviews the cellular and molecular characteristics of embryonic stem cells, induced pluripotent stem cells, neural stem cells, retinal stem/progenitor cells, mesenchymal stem/stromal cells, and their derivatives in vivo and in vitro as sources for regenerative therapy. These cells have all been considered as candidates to treat several major neurological disorders and diseases, owing to their self-renewal capacity, multi-directional differentiation, neurotrophic properties, and immune modulation effects. We also review representative basic research and recent clinical trials using stem cells for neurodegenerative diseases, including Parkinson’s disease, Alzheimer’s disease, and age-related macular degeneration, as well as traumatic brain injury and glioblastoma. In spite of a few unsuccessful cases, risks of tumorigenicity, and ethical concerns, most results of animal experiments and clinical trials demonstrate efficacious therapeutic effects of stem cells in the treatment of nervous system disease. In summary, these emerging findings in regenerative medicine are likely to contribute to breakthroughs in the treatment of neurological disorders. Thus, stem cells are a promising candidate for the treatment of nervous system diseases.

Ginsenosides: A Potential Neuroprotective Agent.

Ginseng is a traditional Chinese medicine with a wide range of pharmacological activities. Ginsenosides are the major constituents of ginseng. Ginsenosides have the unique biological activity and medicinal value, such as antitumor, anti-inflammatory, antioxidation, and inhibition of cell apoptosis. With the increase of stress in life, the incidence of nervous system diseases is also increasing. Neurological diseases pose a huge burden on people's life and health. In recent years, some studies have shown that ginsenosides have a certain role in the prevention and treatment of neurological diseases. However, the research is still in its infancy, and the relevant mechanisms are complex. In the paper, we review the effects and mechanisms of ginsenosides on epilepsy, depression, cerebral ischemia reperfusion injury, Alzheimer's disease, and Parkinson's disease. We hope to provide a theoretical basis for the treatment of nervous system diseases by ginsenosides.

Orexin-A protects SH-SY5Y cells against H2O2-induced oxidative damage via the PI3K/MEK1/2/ERK1/2 signaling pathway.

Orexin-A elicits multiple potent effects on a variety of tumor cells via different signaling pathways. However, it is unknown whether it has a neuroprotective effect on SH-SY5Y human neuroblastoma cells. This study investigated the neuroprotective effect of Orexin-A against hydrogen peroxide (H2O2)-induced oxidative damage in SH-SY5Y cells and the underlying mechanism. H2O2 treatment decreased the viability of SH-SY5Y cells, induced apoptosis, and decreased superoxide dismutase activity. Orexin-A attenuated these effects, indicating that it protects SH-SY5Y cells against H2O2-induced oxidative damage. Pre-treatment with Orexin-A also attenuated H2O2-induced increases in phosphorylation of MEK1/2 and ERK1/2. Moreover, these effects of Orexin-A were reduced in the presence of the PI3K inhibitor LY294002. Finally, pre-treatment with LY294002 abrogated attenuation of the H2O2-induced decrease in cell viability and increase in caspase-3/7 activity by Orexin-A. These results show that the PI3K/MEK1/2/ERK1/2 signaling pathway is involved in the neuroprotective effects of Orexin-A against H2O2-induced oxidative damage in SH-SY5Y cells. Our findings provide insight into the neuroprotective effects of Orexin-A and the underlying mechanism, which will be useful for the treatment of nervous system diseases.

Occurrence of pathogenic and endophytic fungi and their influence on quality of medicinal plants applied in management of neurological diseases and mental disorders

Summary Due to increasing demand of medicinal plants (MPs), quality and safety more attention to the plant health should be paid. Among herb pathogens, especially fungi cause serious diseases in these plants decreasing yield and quality of herbal raw material. Some species, i.e. Fusarium sp., Alternaria sp., Penicillium sp. are known as mycotoxin producers. Paradoxically, self-treatment with herbal raw material can expose the patient to mycotoxin activity. In tissues of some MPs species, asymptomatically endophytic fungi residue. It is known that they are able to influence a biosynthesis of secondary metabolites in their host plant or produce biologically active compounds. Until recently these microorganisms have been neglected as a component of MPs, the reason why there have unexplored bioactivity and biodiversity. The paper presents an overview of herbal plants that are used in the treatment of nervous system diseases. Pathogenic fungi that infect these plants are described. It focused mainly on species producing harmful mycotoxins. The publication presents a list of these mycotoxins and a brief description of their effects on human health. The second part of this article provides information on the occurrence of endophytic fungi in herbal plants and their effects on human health. Coexistence of fungi and medicinal plants is not fully understood but can be crucial to ensure health and safety of patients with neurological diseases and mental disorders.

Retrospect and prospect of the laboratory examination of cerebrospinal fluid

Laboratory tests of cerebrospinal fluid has a long history and multiple service items. It has a positive guiding value in the diagnosis and treatment of central nervous system diseases. With the deepening of people′s understanding of the nervous system diseases, the examination items have developed from single to diversity, from the initial medical examination to biochemistry, molecular biology exams, from the cell, protein level to the gene, molecular level. The main tests include morphology, protein and molecular test levels.This artide will give a systematic introduction of the test items to make readers form a whole understanding of the development process of cerebrospinal fluid laboratory examination.(Chin J Lab Med, 2017, 40: 911-915) Key words: Cerebrospinal fluid; Clinical laboratory techniques; Biological markers; Retrospective studies

Neural stem/progenitor cells on collagen with anchored basic fibroblast growth factor as potential natural nerve conduits for facial nerve regeneration.

Neural stem/progenitor cells (NS/PCs) were beneficial for the treatment of nervous system diseases. However, after transplantation, the beneficial was limited because the number of living NS/PCs decreased rapidly due to insufficient signaling molecules, such as growth factors, in the microenvironments surrounding transplanted cells. In the present study, we constructed collagen-based nerve conduit with anchored bFGF to achieve higher numbers of NS/PCs for repairing facial nerve injury. Compared with other methods involving neutral salt treatment or dialysis, the fabrication method of collagen scaffolds was simple, low-cost and safe, requiring a relatively short time to prepare. At 12weeks after transplantation, the functional and histological results of natural nerve conduits treated group showed significant similarities to the gold standard method of nerve autografting.

Clinical/Therapeutic Approaches for Cannabinoid Ligands in Central and Peripheral Nervous System Diseases: Mini Review.

Cannabinoids, the components of Cannabis sativa Linnaeus, interact with CB1 and CB2 receptors, which are located both in the central nervous system and in the periphery and thus may exert a widespread biological activity in the body. The main medicinal properties of cannabinoids include analgesic, anti-inflammatory, antitumor, appetite stimulation, antiemesis, and muscle relaxation effects. This mini review aims to explore existing clinical trials that investigated the use of cannabinoids in diseases affecting the nervous system. We reviewed recent studies of cannabinoid-based therapy for disorders affecting central and peripheral nervous system in human subjects. There is evidence that cannabinoid-based drugs may effectively control some symptoms associated with nervous system dysfunction, especially various types of pain and neurologic disorders, although studies are limited. The efficacy of cannabinoid drugs in the treatment of nervous system diseases should be verified in future large-scale randomized clinical trials.

Effects of ganglioside GM1 and neural growth factor on neural stem cell proliferation and differentiation.

Neurogenesis, recovery from nerve injury, neurodegeneration, and Parkinson's disease affect people's health, yet the underlying molecular mechanisms remain elusive. Here, we investigated the effect of ganglioside GM1 and neural growth factor (NGF) on neural stem cell (NSC) proliferation and differentiation in vitro to provide a scientific basis for comprehensive treatment of nervous system diseases via NSC application. As widely applied methods of relatively high accuracy, cell counts and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assays were used to assess NSC proliferation. In addition, western blotting was employed to determine NSC differentiation. Cell counts and MTT assays demonstrated that in epidermal growth factor (EGF)- and basic fibroblast growth factor (bFGF)-containing medium, a high concentration of GM1, but not NGF, significantly elevated NSC proliferation. In NSC cultures lacking EGF and bFGF, cell counts and MTT values were significantly increased compared to those in the negative control group on days 4, 7, and 10 after GM1 (25, 100, and 200 ng/mL) but not NGF (25, 50, 100, and 200 ng/mL) treatment. Western blotting revealed significantly increased expression of nestin (an NSC marker) in NSCs treated with GM1, and upregulation of glial fibrillary acidic protein (a glial cell marker) and neuron-specific enolase (a neuron marker) in those administered NGF. Our results suggest that GM1 and NGF induce NSC proliferation and differentiation, respectively, in a dose-dependent manner.

Construction of a novel inducing system with multi-layered alginate microcapsules to regulate differentiation of neural precursor cells from bone mesenchymal stem cells

Neural precursor cells (NPCs) are a promising cell source for the treatment of nervous system diseases; however, they are limited in their applications due to source-related ethical considerations or legislations. Therefore, a novel approach is necessary to obtain sufficient NPCs. Recently, the usage of bone marrow-derived mesenchymal stem cells (BMSCs) differentiated into neural cells has become a potential method to obtain NPCs. Moreover, growth factors (GFs) are emerging as inducers to evoke the differentiation of BMSCs into NPCs. For example, GFs may activate various signaling pathways related to neural differentiation, such as phosphatidylinositol 3 kinase/protein kinase B, cyclic adenosine monophosphate/protein kinase A, and Janus kinase/signal transducer activator of transcription. However, the utilization of growth factors still has some limitations such as high costs and low rates of neural differentiation. Neuroblastoma cells have been characterized as a potential pool for growth factors. Additionally, basic fibroblast growth factor (bFGF), a type of growth factor, has been demonstrated to be able to increase the differentiation and survival rate of NPCs. For better use of neuroblastoma cells and bFGF, we established a novel system involving multi-layered alginate-polylysine-alginate (APA) microcapsules to encapsulate neuroblastoma cells and bFGF, which may not only provide sufficient growth factors in a sustained manner but also avoid the carcinogenicity caused by neuroblastoma cells. Above all, we hypothesized that neuroblastoma cells and bFGF encapsulated in multilayered alginate microcapsules may efficiently induce the differentiation of BMSCs into NPCs.

Neonatal Atlas Templates for the Study of Brain Development Using Magnetic Resonance Images

The quantification of neonatal brain development has a significant role in understanding, prevention, diagnosis and treatment of nervous system diseases in infancy time. On the other hand, brain development and its morphological changes are very fast during the first weeks after birth. So, age-related brain atlases representing sharp anatomical features of a neonatal population are indispensable. In this paper, we constructed two neonatal brain atlases for the age ranges of 39-40 and 41-42 weeks' gestational age with 16 T1-weighted magnetic resonance images using an improved groupwise registration. Neonatal images were normalized to the newly created and previously available neonatal atlases. The similarity between these atlases and normalized images was calculated via mutual information. The mean of mutual information between normalized images and the new atlases using the proposed algorithm is larger. This result confirms the greater similarity between normalized images and the atlases created in this paper. Besides, neonatal brain development was analyzed using deformation based morphometry and brain anatomical changes could be seen in local regions. Keywords: Deformation based morphometry, groupwise registration, magnetic resonance imaging, morphological brain development analysis, neonatal brain atlas.

Flexible endoscopy in neurosurgery

Endoscopic neurosurgery is a new and extremely promising area in surgical treatment of nervous system diseases. The advantages of the technique are associated with decreased severity of a surgical trauma due to a smaller approach, but with the preserved amount of performed manipulations. The article presents the first results of application of flexible endoscopy in the surgical treatment of diseases of the brain and spinal cord. A high efficacy of this high-tech approach and a significantly lower rate of complications compared to open surgery are demonstrated.