Progress in the Treatment of Central Nervous System Diseases Based on Nanosized Traditional Chinese Medicine.

Traditional Chinese Medicine (TCM) is widely used in clinical practice to treat diseases related to central nervous system (CNS) damage. However, the blood-brain barrier (BBB) constitutes a significant impediment to the effective delivery of TCM, thus substantially diminishing its efficacy. Advances in nanotechnology and its applications in TCM (also known as nano-TCM) can deliver active ingredients or components of TCM across the BBB to the targeted brain region. This review provides an overview of the physiological and pathological mechanisms of the BBB and systematically classifies the common TCM used to treat CNS diseases and types of nanocarriers that effectively deliver TCM to the brain. Additionally, drug delivery strategies for nano-TCMs that utilize in vivo physiological properties or in vitro devices to bypass or cross the BBB are discussed. This review further focuses on the application of nano-TCMs in the treatment of various CNS diseases. Finally, this article anticipates a design strategy for nano-TCMs with higher delivery efficiency and probes their application potential in treating a wider range of CNS diseases.

Modulating the polarization phenotype of microglia - A valuable strategy for central nervous system diseases.

Central nervous system (CNS) diseases have become one of the leading causes of death in the global population. The pathogenesis of CNS diseases is complicated, so it is important to find the patterns of the disease to improve the treatment strategy. Microglia are considered to be a double-edged sword, playing both harmful and beneficial roles in CNS diseases. Therefore, it is crucial to understand the progression of the disease and the changes in the polar phenotype of microglia to provide guidance in the treatment of CNS diseases. Microglia activation may evolve into different phenotypes: M1 and M2 types. We focused on the roles that M1 and M2 microglia play in regulating intercellular dialogues, pathological reactions and specific diseases in CNS diseases. Importantly, we summarized the strategies used to modulate the polarization phenotype of microglia, including traditional pharmacological modulation, biological therapies, and physical strategies. This review will contribute to the development of potential strategies to modulate microglia polarization phenotypes and provide new alternative therapies for CNS diseases.

The use of respiratory muscle training in patients with pulmonary dysfunction, internal diseases or central nervous system disorders: a systematic review with meta-analysis.

OBJECTIVE: The aim of this systematic review with meta-analysis was to evaluate the effectiveness of RMT in internal and central nervous system disorders, on pulmonary function, exercise capacity and quality of life. METHODS: The inclusion criteria were (1) publications designed as Randomized Controlled Trial (RCT), with (2) participants being adults with pulmonary dysfunction caused by an internal disease or central nervous system disorder, (3) an intervention defined as RMT (either IMT or EMT) and (4) with the assessment of exercise capacity, respiratory function and quality of life. For the methodological quality assessment of risk of bias, likewise statistical analysis and meta-analysis the RevMan version 5.3 software and the Cochrane Risk of Bias Tool were used. Two authors independently analysed the following databases for relevant research articles: PubMed, Scopus, Cochrane Library, Web of Science, and Embase. RESULTS: From a total of 2200 records, the systematic review includes 29 RCT with an overall sample size of 1155 patients. Results suggest that patients with internal and central nervous system disorders who underwent RMT had better quality of life and improved significantly their performance in exercise capacity and in respiratory function assessed with FVC and MIP when compared to control conditions (i.e. no intervention, sham training, placebo or conventional treatments). CONCLUSION: Respiratory muscle training seems to be more effective than control conditions (i.e. no intervention, sham training, placebo or conventional treatment), in patients with pulmonary dysfunction due to internal and central nervous system disorders, for quality of life, exercise capacity and respiratory function assessed with MIP and FVC, but not with FEV1.

Central pain syndromes.

The management of pain in persons with neurological injuries is challenging and complex. A holistic view and clinical approach are necessary when addressing pain in patients with neurological impairment because interpreting signs and symptoms and deciphering sources of pain is never a straightforward process. This problem is further magnified with the management of central pain syndromes. The best approach is to have a good understanding of the clinical characteristics commonly found in this patient population, in particular for patients with stroke, multiple sclerosis (MS), or spinal cord injury (SCI), as central pain manifests differently between these groups. This paper will focus on the history, clinical presentation, pathophysiology, assessment, and treatment of central pain in patients with these types of neurological conditions. In addition to being at risk for a decline in quality of life, patients with pain syndromes are also prone to adverse responses to treatments (e.g., opioid addiction). It is therefore important to methodically analyze the similarities and differences between patients with different pain syndromes.

Sarcoidosis of the central nervous system: Safety and efficacy of treatment, and experience of biological therapies.

OBJECTIVES: Neurological complications of sarcoidosis are uncommon and the natural history and optimal treatments under-researched. With the advent of biological therapies, it is important to define the clinical characteristics and immunopathology of the disease. PATIENTS AND METHODS: Patients referred to and treated within the Centre for Neurosarcoidosis over a 15 year period who had biopsy proven "highly probable" disease of the central nervous system were studied prospectively. RESULTS: Corticosteroids were used effectively in all patients, immunosuppression in 79 % and TNFα antagonists in 23 %. Treatment with steroids alone inevitably led to relapse, and low dose immunosuppression was ineffective in those with severe forms of the disease. Use of biological therapies substantially improved outcome. Patients with cranial neuropathy had an excellent outcome. Those with pachymeningitis had marked radiological abnormalities but less disablement. Those with leptomeningitis had an invasive, destructive disease which responded well to treatment but with residual neurological impairments. Treatment was required for many years, but the risk of relapse following treatment withdrawal was low. Infective complications arose in six. There were two deaths, neither directly related to the neurological disease, nor its treatment. CONCLUSIONS: This prospective study of the natural history and treatment response in neurosarcoidosis provides evidence that the use of high dose immunosuppression and early and prolonged use of biological therapies is associated with greatly improved outcomes and lower mortality. The data may be used to plan further studies and treatment trials, and provide class IV evidence for the effectiveness of biological agents in the treatment of Neurosarcoidosis.

Electrical stimulation of cranial nerves in cognition and disease.

The cranial nerves are the pathways through which environmental information (sensation) is directly communicated to the brain, leading to perception, and giving rise to higher cognition. Because cranial nerves determine and modulate brain function, invasive and non-invasive cranial nerve electrical stimulation methods have applications in the clinical, behavioral, and cognitive domains. Among other neuromodulation approaches such as peripheral, transcranial and deep brain stimulation, cranial nerve stimulation is unique in allowing axon pathway-specific engagement of brain circuits, including thalamo-cortical networks. In this review we amalgamate relevant knowledge of 1) cranial nerve anatomy and biophysics; 2) evidence of the modulatory effects of cranial nerves on cognition; 3) clinical and behavioral outcomes of cranial nerve stimulation; and 4) biomarkers of nerve target engagement including physiology, electroencephalography, neuroimaging, and behavioral metrics. Existing non-invasive stimulation methods cannot feasibly activate the axons of only individual cranial nerves. Even with invasive stimulation methods, selective targeting of one nerve fiber type requires nuance since each nerve is composed of functionally distinct axon-types that differentially branch and can anastomose onto other nerves. None-the-less, precisely controlling stimulation parameters can aid in affecting distinct sets of axons, thus supporting specific actions on cognition and behavior. To this end, a rubric for reproducible dose-response stimulation parameters is defined here. Given that afferent cranial nerve axons project directly to the brain, targeting structures (e.g. thalamus, cortex) that are critical nodes in higher order brain networks, potent effects on cognition are plausible. We propose an intervention design framework based on driving cranial nerve pathways in targeted brain circuits, which are in turn linked to specific higher cognitive processes. State-of-the-art current flow models that are used to explain and design cranial-nerve-activating stimulation technology require multi-scale detail that includes: gross anatomy; skull foramina and superficial tissue layers; and precise nerve morphology. Detailed simulations also predict that some non-invasive electrical or magnetic stimulation approaches that do not intend to modulate cranial nerves per se, such as transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS), may also modulate activity of specific cranial nerves. Much prior cranial nerve stimulation work was conceptually limited to the production of sensory perception, with individual titration of intensity based on the level of perception and tolerability. However, disregarding sensory emulation allows consideration of temporal stimulation patterns (axon recruitment) that modulate the tone of cortical networks independent of sensory cortices, without necessarily titrating perception. For example, leveraging the role of the thalamus as a gatekeeper for information to the cerebral cortex, preventing or enhancing the passage of specific information depending on the behavioral state. We show that properly parameterized computational models at multiple scales are needed to rationally optimize neuromodulation that target sets of cranial nerves, determining which and how specific brain circuitries are modulated, which can in turn influence cognition in a designed manner.

Hyperbaric oxygen therapy in fibromyalgia and the diseases involving the central nervous system.

OBJECTIVES: This paper briefly describes the therapeutic mechanisms underlying hyperbaric oxygen therapy (HBOT), and reviews data concerning its effects and efficacy in Parkinson's disease (PD) and fibromyalgia (FM). METHODS: The studies included in this review all evaluated the effect of HBOT in patients with diseases involving CNS. The PubMed databases were searched from 1980 to September 2019 using the keywords: 'hyperbaric oxygen therapy', 'fibromyalgia' and 'Parkinson's disease'. RESULTS: HBOT is already indicated in various diseases and is the subject of continuous research and development. Data from models of PD show that it may play a neuroprotective role because of its ability to reduce oxidative stress and neurodegeneration, and protect against neuronal apoptosis. It is effective in improving the symptoms and quality of life of fibromyalgia patients, and rectifies abnormal brain activity in pain-related areas. Evidence from animal studies supports its use as an alternative treatment for other rheumatic diseases as it alleviates pain and reduces inflammation. CONCLUSIONS: Data mainly from animal studies support the use of HBOT in the treatment of PD and rheumatic diseases, but further work is necessary to clarify its therapeutic role in patients with these chronic disorders.

African Plants with Antidiabetic Potentials: Beyond Glycaemic Control to Central Nervous System Benefits.

BACKGROUND: For centuries, humans have used medicinal plants in the management of both acute and chronic diseases. Currently, the practice of using medicinal plants to manage diseases is becoming increasingly-common; especially in medium to low-income economies where the cost of, or ease of access to orthodox medications are limitations to their effective and sustained use. Diabetes mellitus is a chronic disease whose prevalence continues to increase worldwide. An aspect of diabetes mellitus that causes significant morbidity is its neurological complications, which are known to be associated with an enormous economic burden and reduction in quality of life. OBJECTIVES: While research continues to demonstrate that a wide range of plants that are indigenous to Africa have significant antihyperglycaemic properties, scientific information on the neurobehavioural and/or neuromorphological effects of these plants appear to be lacking. Also, their possible benefits in the prevention or amelioration of the neurological complications of diabetes mellitus remain generally unexamined. METHODOLOGY: In this narrative review, we the examine available scientific literature dealing with the neurobehavioural and/or neuromorphological profiles of selected African plants with substantiated antihyperglycaemic properties; aiming to highlight their potential applications in the prevention and management of the neurological complications of diabetes mellitus. RESULTS: This review demonstrates that a number of the African plants with antidiabetic properties also exhibit central nervous system effects. CONCLUSION: While the neurobehavioural and neuromorphological effects of some of these plants had been investigated in animal models of DM; their possible roles in the prevention or amelioration of the neurological complications of DM are yet to be established.

Hyperbaric medicine simulation education curriculum: CNS toxicity during Treatment Table 6 and intubated ICU patient with mucous plugging.

INTRODUCTION/BACKGROUND: The incidence of complications and number of critically ill patients in hyperbaric medicine is relatively low [1]. This poses a challenge to those tasked with educating trainees as well as maintaining the skills of staff. Hyperbaric medicine fellows may not be exposed to critical patient scenarios or complications of hyperbaric medicine during a one-year fellowship. Additional staff may be unfamiliar with these situations as well. The purpose of hyperbaric simulation curriculum is to train health care providers for rare situations. To our knowledge, this hyperbaric simulation curriculum is the first published use of simulation education in the specialty of undersea and hyperbaric medicine. MATERIALS AND METHODS: Two simulation cases have been developed that involve a patient with oxygen toxicity during hyperbaric treatment as well as an ICU patient with mucous plugging. RESULTS: Medical training simulations are an effective method of teaching content and training multiple roles in Undersea and Hyperbaric Medicine. SUMMARY/CONCLUSIONS: A hyperbaric simulation curriculum is an achievable educational initiative that is able to train multiple team members simultaneously in situations that they may not encounter on a regular basis. We believe that this could be easily exported to otherinstitutions for further education.

[Effect of animal medicines for "extinguishing wind to arrest convulsions" on central nervous system diseases].

The human health is seriously affected by central nervous system(CNS) diseases, but the pathogenesis of CNS diseases is still not completely clear. Currently, the drugs used to treat CNS diseases are mainly receptor modulators and neurotransmitter inhibitors, which have serious side effects; and there are short of drugs for treating CNS diseases clinically. Studies suggest that animal medicines mainly include protein, polypeptide and small-molecule compounds, and have such pharmacological effects in calming, resisting convulsions and improving brain tissues. Plenty of studies suggest that animal medicines usually have a strong activity and good curative effect on these diseases, with a promising prospect in research and development of drugs treating CNS diseases. Based on systematic reviews of literatures, this paper summarizes active ingredients and main pharmacological effects of animal medicines in "extinguishing wind to arrest convulsions" for the CNS diseases, epilepsy and cerebral ischemia, and discusses their study value and application prospects. The results showed that the studies of protein and peptides were relatively simple, and some animal medicines were still blank. The authors believed that amino acids and small molecular compounds should be transferred to oligopeptide, advanced protein extraction and separation techniques shall be adopted for identifying the protein polypeptide composition structure and studying the efficacy, and the methods of biological technology were used to develop peptide biological products for the treatment of CNS diseases. This paper could provide ideas and reference for developing animal medicine products for the treatment of CNS diseases.

Neuroprotective Effects of Drug-Induced Therapeutic Hypothermia in Central Nervous System Diseases.

OBJECTIVE: This review article focuses on the neuroprotective effect of drug-induced hypothermia in cerebrovascular diseases and discusses its related side effects. METHOD: A systematic literature search was performed using Pubmed and Embase electronic databases for a retrospective analysis. RESULTS: Experimental studies have shown that drug-induced hypothermia alleviates brain damage and plays a neuroprotective role, thereby reducing mortality and ameliorating neurological deficits. Therefore, drug-induced hypothermia has an important research value and is worth further consideration in the clinical setting. However, drug-induced hypothermia is also associated with side effects, such as ventricular tachycardia, ventricular fibrillation, suppressed immune function, infection, electrolyte imbalance, glucose metabolism disorders, and skeletal muscle tremor. Existing drugs with cooling effects belong to the following categories: (1) dopamine receptor agonists; (2) cannabis; (3) opioid receptors; (4) vanilloid receptors; (5) vasopressins (potent neurotensin receptor agonists); (6) thyroid drugs; (7) adenosine drugs; and (8) purine drugs.

Preventive and Protective Roles of Dietary Nrf2 Activators Against Central Nervous System Diseases.

Central nervous system diseases are major health issues and are often associated with disability or death. Most central nervous system disorders are characterized by high levels of oxidative stress. Nuclear factor erythroid 2 related factor (Nrf2) is known for its ability to regulate the expression of a series of enzymes with antioxidative, prosurvival, and detoxification effects. Under basal conditions, Nrf2 forms a complex with Kelch-like ECH associated protein 1, leading to Nrf2 inactivation via ubiquitination and degradation. However, following exposure of Keap1 to oxidative stress, Nrf2 is released from Keap1, activated, and translocated into the nucleus. Upon nuclear entry, Nrf2 binds to antioxidant response elements (ARE), thereby inducing the expression of genes such as glutathione s-transferase, heme oxygenase 1, and NADPH quinine oxidoreductase 1. Many dietary phytochemicals have been reported to activate the protective Nrf2/ARE pathway. Here, we review the preventive and protective effects of dietary Nrf2 activators against CNS diseases, including stroke, traumatic brain injury, Alzheimer's disease, and Parkinson's disease.

"Quantum Leap" in Photobiomodulation Therapy Ushers in a New Generation of Light-Based Treatments for Cancer and Other Complex Diseases: Perspective and Mini-Review.

OBJECTIVE: Set within the context of the 2015 International Year of Light and Light-Based Technologies,and of a growing and aging world population with ever-rising healthcare needs, this perspective and mini-review focuses on photobiomodulation (PBM) therapy as an emerging, cost-effective, treatment option for cancer (i.e., solid tumors) and other complex diseases, particularly, of the eye (e.g., age-related macular degeneration, diabetic retinopathy, glaucoma, retinitis pigmentosa) and the central nervous system (e.g., Alzheimer's and Parkinson's disease). BACKGROUND DATA: Over the last decades, primary and secondary mechanisms of PBM have been revealed. These include oxygen-dependent and oxygen-independent structural and functional action pathways. Signal and target characteristics determine biological outcome, which is optimal (or even positive) only within a given set of parameters. METHODS: This study was a perspective and nonsystematic literature mini-review. RESULTS: Studies support what we describe as a paradigm shift or "quantum leap" in the understanding and use of light and its interaction with water and other relevant photo-cceptors to restore physiologic function. CONCLUSIONS: Based on existing evidence, it is argued that PBM therapy can raise the standard of care and improve the quality of life of patients for a fraction of the cost of many current approaches. PBM therapy can, therefore,benefit large, vulnerable population groups, including the elderly and the poor, whilehaving a major impact on medical practice and public finances.

Music therapy in neurological rehabilitation settings.

The neurologic music therapy is a new scope of music therapy. Its techniques deal with dysfunctions resulting from diseases of the human nervous system. Music can be used as an alternative modality to access functions unavailable through non-musical stimulus. Processes in the brain activated by the influence of music can be generalized and transferred to non-musical functions. Therefore, in clinical practice, the translation of non-musical therapeutic exercises into analogous, isomorphic musical exercises is performed. They make use of the executive peculiarity of musical instruments and musical structures to prime, cue and coordinate movements. Among musical components, a repetitive rhythm plays a significant role. It regulates physiologic and behavioural functions through the mechanism of entrainment (synchronization of biological rhythms with musical rhythm based on acoustic resonance). It is especially relevant for patients with a deficient internal timing system in the brain. Additionally, regular rhythmic patterns facilitate memory encoding and decoding of non-musical information hence music is an efficient mnemonic tool. The music as a hierarchical, compound language of time, with its unique ability to access affective/motivational systems in the brain, provides time structures enhancing perception processes, mainly in the range of cognition, language and motor learning. It allows for emotional expression and improvement of the motivation for rehabilitation activities. The new technologies of rhythmic sensory stimulation (i.e. Binaural Beat Stimulation) or rhythmic music in combination with rhythmic light therapy appear. This multimodal forms of stimulation are used in the treatment of stroke, brain injury, dementia and other cognitive deficits. Clinical outcome studies provide evidence of the significant superiority of rehabilitation with music over the one without music.

[The evaluation of the effectiveness of electrophoresis in the form of Polymineral wipes on the basis of iodine- bromine natural water in the young children suffering from the consequences of perinatal lesions in the central nervous system].

UNLABELLED: The background: the increased frequency of serious consequences of perinatal lesions in the central nervous system of the young children dictates the necessity to develop the effective methods of physiotherapy for the early-stage rehabilitation of such patients on the basis of an objective assessment of the adaptive reserves of the organism. MATERIAL AND METHODS: The present study involved 53 children at the age from 1 to 12 months presenting with the consequences of perinatal lesions to the central nervous system. Thirty of the children were treated with the use of electrophoresis in the form of Polymineral wipes on the basis of natural iodine-bromine water. The group of comparison was comprised of 23 children treated without physiotherapy. We estimated the clinical effectiveness and the level of adaptive resources based on the results of blood count measurements (the type of non-specific adaptive reaction and the reactivity level); in addition, the electro-acupuncture test was carried out with the use of the hardware-software complex for bioresonance (MOR) therapy. RESULTS: The clinical effectiveness of an electrophoresis in the form of Polymineral wipes on the basis of natural iodine-bromine water used for the treatment of the newborn infants with the consequences of perinatal lesions to the central nervous system amounted to 93.3%. The rearrangement of the adaptive reactions was apparent as the increase in the proportion of the antistress reactions from 63.3% to 86.7%, the decrease in the frequency of the reactivation reaction by a factor of 3.7, and the reduction of the reactivity level by a factor of 3.0. The repeated study with the use of the MORA-test revealed normalization of the altered indicators in all the children with the initially reduced or enhanced values of these indicators. In the comparison group, dynamics of clinical symptoms was less apparent, and the assessment of the adaptative resources revealed their decrease in 78.3% of the cases. CONCLUSION: The present study confirmed the beneficial effect of electrophoresis in the form of Polymineral wipes on the basis of natural iodine-bromine natural water on the dynamics of clinical symptoms and adaptive reserves in the infants suffering from the consequences of perinatal lesions to the central nervous system. The determination of the type of the nonspecific adaptive reaction and the level of reactivity in combination with the MORA-test can be a method for the assessment of the effectiveness and adequacy of physiotherapeutic modalities for the young children.

DTI-based deterministic fibre tracking of the medial forebrain bundle.

BACKGROUND: Deep brain stimulation (DBS) of the medial forebrain bundle (MFB) was reported to reduce symptoms in psychiatric disorders. The aim of our study was to find standardised parameters for diffusion tensor imaging (DTI) based fibre tracking to reliably visualise the MFB. METHODS: Twenty-two cerebral hemispheres in 11 patients were investigated. Three different regions of interest (ROIs) were defined as seed regions for fibre tracking: the ipsilateral and contralateral superior cerebellar peduncle (SCP) and the nucleus raphe dorsalis (NRD). From each seed region the fibres were followed separately through the ventral tegmental area (VTA = second ROI) and their further courses and volumina were documented and compared. Minimal fibre length was set at 30 mm and the FA threshold at 0.12. RESULTS: The fibre tracts starting in seed regions in the ipsilateral SCP and the NRD follow a similar course along the lateral wall of the third ventricle (hypothalamus) and the anterior limb of the internal capsule (ALIC) to inferior fronto-medial brain areas. These fibres are in accordance with the course of the MFB as described in various anatomical atlases. Consistently, a branch leaves the main fibre tract laterally to take a course through the capsula externa to the temporo-parietal cortex. Fibre tracts starting from the contralateral SCP follow a more superior and lateral course, including the dentato-rubro-thalamic and the pyramidal tract. CONCLUSIONS: Deterministic fibre tracking with standardised ROIs provides constant and reproducible delineations of the medial forebrain bundle. Its visualisation might help to adjust targeting in DBS for psychiatric disorders.

[Neurological diseases and nutrition -- what can we do?]. / Neurológiai kórképek és táplálás -- Mit tehetünk?

Neurological diseases and nutrition are in complex relationship. In the first part of this review the nutritional consequences of acute neurological diseases is presented, with special emphasis on traumatic injuries of the nervous system and stroke. Nutritional therapy of these patients is described in detail. In addition, chronic, degenerative neurological pathological conditions are also discussed, including nutritional consequences and possibilities of therapy. Some ethical and legal issues are also considered. The second part of this review article describes neurological consequences of nutritional problems, both deficits of macro- and micronutrients and toxic effects.

tDCS-enhanced motor and cognitive function in neurological diseases.

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation tool that is now being widely used in neuroscientific and clinical research in humans. While initial studies focused on modulation of cortical excitability, the technique quickly progressed to studies on motor and cognitive functions in healthy humans and in patients with neurological diseases. In the present review we will first provide the reader with a brief background on the basic principles of tDCS. In the main part, we will outline recent studies with tDCS that aimed at enhancing behavioral outcome or disease-specific symptoms in patients suffering from mild cognitive impairment, Alzheimer's disease, movement disorders, and epilepsy, or persistent deficits after stroke. The review will close with a summary statement on the present use of tDCS in the treatment of neurological disorders, and an outlook to further developments in this realm. tDCS may be an ideal tool to be administered in parallel to intensive cognitive or motor training in neurological disease, but efficacy for the areas of activities and participation still needs to be established in controlled randomized trials. Its use in reducing disease-specific symptoms like dystonia or epileptic seizures is still unclear.