RESUMO
INTRODUCTION: Human neurodevelopmental and neurodegenerative diseases (NDevDs and NDegDs, respectively) encompass a broad spectrum of disorders affecting the nervous system with an increasing incidence. In this context, the nematode C. elegans, has emerged as a benchmark model for biological research, especially in the field of neuroscience. AREAS COVERED: The authors highlight the numerous advantages of this tiny worm as a model for exploring nervous system pathologies and as a platform for drug discovery. There is a particular focus given to describing the existing models of C. elegans for the study of NDevDs and NDegDs. Specifically, the authors underscore their strong applicability in preclinical drug development. Furthermore, they place particular emphasis on detailing the common techniques employed to explore the nervous system in both healthy and diseased states. EXPERT OPINION: Drug discovery constitutes a long and expensive process. The incorporation of invertebrate models, such as C. elegans, stands as an exemplary strategy for mitigating costs and expediting timelines. The utilization of C. elegans as a platform to replicate nervous system pathologies and conduct high-throughput automated assays in the initial phases of drug discovery is pivotal for rendering therapeutic options more attainable and cost-effective.
Assuntos
Caenorhabditis elegans , Modelos Animais de Doenças , Desenvolvimento de Medicamentos , Descoberta de Drogas , Doenças Neurodegenerativas , Caenorhabditis elegans/efeitos dos fármacos , Animais , Humanos , Descoberta de Drogas/métodos , Desenvolvimento de Medicamentos/métodos , Doenças Neurodegenerativas/tratamento farmacológico , Doenças Neurodegenerativas/fisiopatologia , Ensaios de Triagem em Larga Escala/métodos , Avaliação Pré-Clínica de Medicamentos/métodos , Transtornos do Neurodesenvolvimento/tratamento farmacológico , Transtornos do Neurodesenvolvimento/fisiopatologia , Doenças do Sistema Nervoso/tratamento farmacológico , Doenças do Sistema Nervoso/fisiopatologiaRESUMO
Background: The incidence of neurological diseases is increasing throughout the world. The aim of the present study was to identify nutrition and microbiome factors related to structural and functional neurological abnormalities to optimize future preventive strategies. Methods: Two hundred thirty-eight patients suffering from (1) structural (neurodegeneration) or (2) functional (epilepsy) neurological abnormalities or (3) chronic pain (migraine) and 612 healthy control subjects were analyzed by validated 12-month food frequency questionnaire (FFQ) and 16S rRNA microbiome sequencing (from stool samples). A binomial logistic regression model was applied for risk calculation and functional pathway analysis to show which functional pathway could discriminate cases and healthy controls. Results: Detailed analysis of more than 60 macro- and micronutrients revealed no distinct significant difference between cases and controls, whereas BMI, insulin resistance and metabolic inflammation in addition to alcohol consumption were major drivers of an overall neurological disease risk. The gut microbiome analysis showed decreased alpha diversity (Shannon index: p = 9.1× 10-7) and species richness (p = 1.2 × 10-8) in the case group as well as significant differences in beta diversity between cases and controls (Bray-Curtis: p = 9.99 × 10-4; Jaccard: p = 9.99 × 10-4). The Shannon index showed a beneficial effect (OR = 0.59 (95%-CI (0.40, 0.87); p = 8 × 10-3). Cases were clearly discriminated from healthy controls by environmental information processing, signal transduction, two component system and membrane transport as significantly different functional pathways. Conclusions: In conclusion, our data indicate that an overall healthy lifestyle, in contrast to supplementation of single micro- or macronutrients, is most likely to reduce overall neurological abnormality risk and that the gut microbiome is an interesting target to develop novel preventive strategies.
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Consumo de Bebidas Alcoólicas/fisiopatologia , Índice de Massa Corporal , Microbioma Gastrointestinal , Doenças do Sistema Nervoso/microbiologia , Doenças do Sistema Nervoso/fisiopatologia , Estudos de Casos e Controles , Estudos de Coortes , Intervalos de Confiança , Ingestão de Energia , Feminino , Humanos , Masculino , Micronutrientes/metabolismo , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/patologia , Nutrientes/metabolismo , Razão de Chances , Análise de Componente Principal , Fatores de Risco , Especificidade da EspécieRESUMO
Icariin is a biologically active substance in Epimedii herba that is used for the treatment of neurologic disorders. However, a comprehensive analysis of the molecular mechanisms of icariin is lacking. In this review, we present a brief history of the use of icariin for medicinal purposes; describe the active chemical components of Epimedii herba; and examine the evidence from experimental studies that have uncovered molecular targets of icariin in different diseases. We also constructed a protein-protein interaction network and carried out Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functional enrichment analyses to predict the therapeutic actions of icariin in nervous system diseases including Alzheimer disease, Parkinson disease, ischemic stroke, depressive disorder, multiple sclerosis, glioblastoma, and hereditary spastic paraplegias. The results of our analyses can guide future studies on the application of icariin to the treatment of neurologic disorders.
Assuntos
Medicamentos de Ervas Chinesas/química , Flavonoides/farmacologia , Doenças do Sistema Nervoso/tratamento farmacológico , Animais , Flavonoides/isolamento & purificação , Humanos , Terapia de Alvo Molecular , Doenças do Sistema Nervoso/fisiopatologia , Farmacologia em Rede , Mapas de Interação de ProteínasRESUMO
The nucleus accumbens core (NAcc) is an important component of brain reward circuitry, but studies have revealed its involvement in pain circuitry also. However, its effect on trigeminal neuralgia (TN) and the mechanism underlying it are yet to be fully understood. Therefore, this study aimed to examine the outcomes of optogenetic stimulation of NAcc GABAergic neurons in an animal model of TN. Animals were allocated into TN, sham, and control groups. TN was generated by infraorbital nerve constriction and the optogenetic virus was injected into the NAcc. In vivo extracellular recordings were acquired from the ventral posteromedial nucleus of the thalamus. Alterations of behavioral responses during stimulation "ON" and "OFF" conditions were evaluated. In vivo microdialysis was performed in the NAcc of TN and sham animals. During optogenetic stimulation, electrophysiological recordings revealed a reduction of both tonic and burst firing activity in TN animals, and significantly improved behavioral responses were observed as well. Microdialysis coupled with liquid chromatography/tandem mass spectrometry analysis revealed significant alterations in extracellular concentration levels of GABA, glutamate, acetylcholine, dopamine, and citrulline in NAcc upon optic stimulation. In fine, our results suggested that NAcc stimulation could modulate the transmission of trigeminal pain signals in the TN animal model.
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Neurônios GABAérgicos/fisiologia , Doenças do Sistema Nervoso/fisiopatologia , Núcleo Accumbens/fisiopatologia , Neuralgia do Trigêmeo/fisiopatologia , Animais , Modelos Animais de Doenças , Dopamina/metabolismo , Feminino , Neurônios GABAérgicos/metabolismo , Ácido Glutâmico/metabolismo , Maxila/inervação , Doenças do Sistema Nervoso/metabolismo , Núcleo Accumbens/metabolismo , Optogenética/métodos , Ratos , Ratos Sprague-Dawley , Recompensa , Tálamo/metabolismo , Neuralgia do Trigêmeo/metabolismoRESUMO
AIM: To explore the breadth of pediatric neurological conditions for which neuromuscular electrical stimulation (NMES) has been studied. METHOD: Databases (PubMed, Google Scholar, Scopus, and Embase) were searched from 2000 to 2020, using the search terms 'neuromuscular electrical stimulation' OR 'functional electrical stimulation' with at least one of the words 'pediatric OR child OR children OR adolescent', and without the words 'dysphagia OR implanted OR enuresis OR constipation'. Articles focused on adults or individuals with cerebral palsy (CP) were excluded. RESULTS: Thirty-five studies met the inclusion criteria, with a total of 353 pediatric participants (293 unique participants; mean age 7y 4mo, range 1wk-38y). NMES was applied in a range of pediatric conditions other than CP, including stroke, spinal cord injury, myelomeningocele, scoliosis, congenital clubfoot, obstetric brachial plexus injury, genetic neuromuscular diseases, and other neuromuscular conditions causing weakness. INTERPRETATION: All 35 studies concluded that NMES was well-tolerated and most studies suggested that NMES could augment traditional therapy methods to improve strength. Outcome measurements were heterogeneous. Further research on NMES with larger, randomized studies will help clarify its potential to improve physiology and mobility in pediatric patients with neuromuscular conditions. What this paper adds Neuromuscular electrical stimulation (NMES) appears to be tolerated by pediatric patients. NMES shows potential for augmenting recovery in pediatric patients with a range of rehabilitation needs.
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Terapia por Estimulação Elétrica/métodos , Doenças do Sistema Nervoso/terapia , Criança , Humanos , Força Muscular/fisiologia , Doenças do Sistema Nervoso/fisiopatologia , Resultado do TratamentoRESUMO
ABSTRACT: The monoterpene glycoside paeoniflorin (PF) is the principal active constituent of the traditional Chinese herbal medicines, Radix Paeoniae Alba and Radix Paeoniae Rubra, which have been used for millennia to treat cardiovascular diseases (eg, hypertension, bleeding, and atherosclerosis) and neurological ailments (eg, headaches, vertigo, dementia, and pain). Recent evidence has revealed that PF exerts inhibitory effects on inflammation, fibrosis, and apoptosis by targeting several intracellular signaling cascades. In this review, we address the current knowledge about the pharmacokinetic properties of PF and its molecular mechanisms of action. We also present results from recent preclinical studies supporting the utility of PF for the treatment of pain, cerebral ischemic injury, and neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases. Moreover, new evidence suggests a general protective role of PF in heart attack, diabetic kidney, and atherosclerosis. Mechanistically, PF exerts multiple anti-inflammatory actions by targeting toll-like receptor-mediated signaling in both parenchymal and immune cells (in particular, macrophages and dendritic cells). A better understanding of the molecular actions of PF may lead to the expansion of its therapeutic uses.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Glucosídeos/farmacologia , Monoterpenos/farmacologia , Animais , Doenças Cardiovasculares/fisiopatologia , Doenças Cardiovasculares/prevenção & controle , Humanos , Nefropatias/fisiopatologia , Nefropatias/prevenção & controle , Doenças do Sistema Nervoso/fisiopatologia , Doenças do Sistema Nervoso/prevenção & controleRESUMO
BACKGROUND: Patients with neurological disorders can present the weakness of respiratory muscle and impaired cough function. Previous studies have shown that respiratory muscle strength training (RMT) is an effective method of improving the strength of respiratory muscle. The effects of RMT on cough function remain controversial. OBJECTIVE: We aimed to analyze randomized controlled trials (RCTs) that investigated the effects of RMT on cough function of patients with neurological disorders. METHODS: Pubmed, Medline, Embase, and the Cochrane Library were searched electronically for RCTs. Two reviewers independently performed data extraction and quality assessment. Data were analyzed by using RevMan 5.3 software of The Cochrane Collaboration. RESULTS: Five studies with 185 participants were included. The mean PEDro score was 6.2 (range 5 to 7), showing moderate methodological quality. Random-effects meta-analyses showed that respiratory muscle training improved peak expiratory cough flow of voluntary cough by 2.16 (95% CI 1.16 to 3.17) and involuntary cough by 2.84 (95% CI 1.29 to 4.39), with statistical significance (Pâ<â0.0001, Pâ=â0.0003). The experimental group had an improvement of 0.19âcmH2O (95% CI -0.12 to 0.5) on the maximal inspiratory pressure, 0.09âcmH2O (95% CI -0.23 to 0.42) on the maximal expiratory pressure, but with no statistical significance (Pâ=â0.23, Pâ=â0.58) between groups. CONCLUSION: Respiratory muscle training was considered as an effective method for improving cough function. However, this review was insufficient to conclude whether respiratory muscle training was effective in improving inspiratory and expiratory muscle strength, this was opposite with previous meta-analysis. These effects might due to the small samples and different diseases.
Assuntos
Exercícios Respiratórios/métodos , Tosse/prevenção & controle , Doenças do Sistema Nervoso/fisiopatologia , Reabilitação Neurológica/métodos , Tosse/fisiopatologia , Expiração , Humanos , Força Muscular , Ensaios Clínicos Controlados Aleatórios como Assunto , Músculos Respiratórios/fisiologiaRESUMO
Riboflavin is classified as one of the water-soluble B vitamins. It is part of the functional group of flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) cofactors and is required for numerous flavoprotein-catalysed reactions. Riboflavin has important antioxidant properties, essential for correct cell functioning. It is required for the conversion of oxidised glutathione to the reduced form and for the mitochondrial respiratory chain as complexes I and II contain flavoprotein reductases and electron transferring flavoproteins. Riboflavin deficiency has been demonstrated to impair the oxidative state of the body, especially in relation to lipid peroxidation status, in both animal and human studies. In the nervous system, riboflavin is essential for the synthesis of myelin and its deficiency can determine the disruption of myelin lamellae. The inherited condition of restricted riboflavin absorption and utilisation, reported in about 10-15% of world population, warrants further investigation in relation to its association with the main neurodegenerative diseases. Several successful trials testing riboflavin for migraine prevention were performed, and this drug is currently classified as a Level B medication for migraine according to the American Academy of Neurology evidence-based rating, with evidence supporting its efficacy. Brown-Vialetto-Van Laere syndrome and Fazio-Londe diseases are now renamed as "riboflavin transporter deficiency" because these are autosomal recessive diseases caused by mutations of SLC52A2 and SLC52A3 genes that encode riboflavin transporters. High doses of riboflavin represent the mainstay of the therapy of these diseases and high doses of riboflavin should be rapidly started as soon as the diagnosis is suspected and continued lifelong. Remarkably, some mitochondrial diseases respond to supplementation with riboflavin. These include multiple acyl-CoA-dehydrogenase deficiency (which is caused by ETFDH gene mutations in the majority of the cases, or mutations in the ETFA and ETFB genes in a minority), mutations of ACAD9 gene, mutations of AIFM1 gene, mutations of the NDUFV1 and NDUFV2 genes. Therapeutic riboflavin administration has been tried in other neurological diseases, including stroke, multiple sclerosis, Friedreich's ataxia and Parkinson's disease. Unfortunately, the design of these clinical trials was not uniform, not allowing to accurately assess the real effects of this molecule on the disease course. In this review we analyse the properties of riboflavin and its possible effects on the pathogenesis of different neurological diseases, and we will review the current indications of this vitamin as a therapeutic intervention in neurology.
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Doenças do Sistema Nervoso/tratamento farmacológico , Riboflavina/uso terapêutico , Animais , Paralisia Bulbar Progressiva/tratamento farmacológico , Paralisia Bulbar Progressiva/genética , Flavoproteínas Transferidoras de Elétrons/genética , Perda Auditiva Neurossensorial/tratamento farmacológico , Humanos , Proteínas de Membrana Transportadoras/genética , Deficiência Múltipla de Acil Coenzima A Desidrogenase/tratamento farmacológico , Deficiência Múltipla de Acil Coenzima A Desidrogenase/genética , Mutação , Doenças do Sistema Nervoso/fisiopatologia , Riboflavina/metabolismoRESUMO
The regulation of energy balance requires the complex integration of homeostatic and hedonic pathways, but sensory inputs from the gastrointestinal (GI) tract are increasingly recognized as playing critical roles. The stomach and small intestine relay sensory information to the central nervous system (CNS) via the sensory afferent vagus nerve. This vast volume of complex sensory information is received by neurons of the nucleus of the tractus solitarius (NTS) and is integrated with responses to circulating factors as well as descending inputs from the brainstem, midbrain, and forebrain nuclei involved in autonomic regulation. The integrated signal is relayed to the adjacent dorsal motor nucleus of the vagus (DMV), which supplies the motor output response via the efferent vagus nerve to regulate and modulate gastric motility, tone, secretion, and emptying, as well as intestinal motility and transit; the precise coordination of these responses is essential for the control of meal size, meal termination, and nutrient absorption. The interconnectivity of the NTS implies that many other CNS areas are capable of modulating vagal efferent output, emphasized by the many CNS disorders associated with dysregulated GI functions including feeding. This review will summarize the role of major CNS centers to gut-related inputs in the regulation of gastric function with specific reference to the regulation of food intake.
Assuntos
Vias Aferentes , Encéfalo/fisiologia , Ingestão de Alimentos , Vias Eferentes , Trato Gastrointestinal/inervação , Trato Gastrointestinal/fisiologia , Tonsila do Cerebelo/fisiologia , Animais , Diabetes Mellitus/fisiopatologia , Hipocampo/fisiologia , Humanos , Hipotálamo/fisiologia , Inflamação/fisiopatologia , Doenças do Sistema Nervoso/fisiopatologia , Obesidade/fisiopatologia , Rombencéfalo/fisiologia , Nervo Vago/fisiologiaRESUMO
The importance of circadian rhythm dysfunctions in the pathophysiology of neurological diseases has been highlighted recently. Chronopharmacology principles imply that tailoring the timing of treatments to the circadian rhythm of individual patients could optimize therapeutic management. According to these principles, chronopharmacology takes into account the individual differences in patients' clocks, the rhythmic changes in the organism sensitivity to therapeutic and side effects of drugs, and the predictable time variations of disease. This review examines the current literature on chronopharmacology of neurological diseases focusing its scope on epilepsy, Alzheimer and Parkinson diseases, and neuropathic pain, even if other neurological diseases could have been analyzed. While the results of the studies discussed in this review point to a potential therapeutic benefit of chronopharmacology in neurological diseases, the field is still in its infancy. Studies including a sufficiently large number of patients and measuring gold standard markers of the circadian rhythmicity are still needed to evaluate the beneficial effect of administration times over the 24-hour day but also of clock modulating drugs.
Assuntos
Cronofarmacoterapia , Doenças do Sistema Nervoso/tratamento farmacológico , Doenças do Sistema Nervoso/fisiopatologia , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/fisiopatologia , Ritmo Circadiano , Esquema de Medicação , Epilepsia/tratamento farmacológico , Epilepsia/fisiopatologia , Humanos , Neuralgia/tratamento farmacológico , Neuralgia/fisiopatologia , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/fisiopatologia , Núcleo Supraquiasmático/metabolismoRESUMO
Atrial fibrillation (AF) is the most commonly diagnosed arrhythmia and eludes an efficacious cure despite an increasing prevalence and a significant association with morbidity and mortality. In addition to an array of clinical sequelae, the origins and propagation of AF are multifactorial. In recent years, the contribution from the autonomic nervous system has been an area of particular interest. This review highlights the relevant physiology of autonomic and neurohormonal contributions to AF origin and maintenance, the current state of the literature on targeted therapies, and the path forward for clinical interventions.
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Fibrilação Atrial , Sistema Nervoso Autônomo/fisiopatologia , Doenças do Sistema Nervoso , Doenças do Sistema Nervoso Autônomo/fisiopatologia , Doenças do Sistema Nervoso Autônomo/terapia , Fatores de Risco de Doenças Cardíacas , Humanos , Doenças do Sistema Nervoso/fisiopatologia , Doenças do Sistema Nervoso/terapia , Sistema Renina-Angiotensina/fisiologia , Estimulação Elétrica Nervosa TranscutâneaRESUMO
3ß,7ß,25-Trihydroxycucurbita-5,23(E)-dien-19-al (TCD) is a triterpenoid isolated from wild bitter gourd that is a common tropical vegetable with neuroprotective effects. Because excessive glutamate release is a major cause of neuronal damage in various neurological disorders, the aims of this study were to examine the effect of TCD on glutamate release in vitro and to examine the effect of TCD in vivo. In rat cerebrocortical synaptosomes, TCD reduced 4-aminopyridine (4-AP)-stimulated glutamate release and Ca2+ concentration elevation, but had no effect on plasma membrane potential. TCD-mediated inhibition of 4-AP-induced glutamate release was dependent on the presence of extracellular calcium; persisted in the presence of the glutamate transporter inhibitor dl-TBOA, P/Q-type Ca2+ channel blocker ω-agatoxin IVA, and intracellular Ca2+-releasing inhibitors dantrolene and CGP37157; and was blocked by the vesicular transporter inhibitor bafilomycin A1 and the N-type Ca2+ channel blocker ω-conotoxin GVIA. Molecular docking studies have demonstrated that TCD binds to N-type Ca2+ channels. TCD-mediated inhibition of 4-AP-induced glutamate release was abolished by the Ca2+-dependent protein kinase C (PKC) inhibitor Go6976, but was unaffected by the Ca2+-independent PKC inhibitor rottlerin. Furthermore, TCD considerably reduced the phosphorylation of PKC, PKCα, and myristoylated alanine-rich C kinase substrate, a major presynaptic substrate for PKC. In a rat model of kainic acid (KA)-induced excitotoxicity, TCD pretreatment substantially attenuated KA-induced neuronal death in the CA3 hippocampal region. These results suggest that TCD inhibits synaptosomal glutamate release by suppressing N-type Ca2+ channels and PKC activity and exerts protective effects against KA-induced excitotoxicity in vivo.
Assuntos
Ácido Glutâmico/metabolismo , Ácido Caínico/efeitos adversos , Momordica charantia/química , Doenças do Sistema Nervoso/tratamento farmacológico , Fármacos Neuroprotetores/administração & dosagem , Extratos Vegetais/administração & dosagem , Sinaptossomos/efeitos dos fármacos , Triterpenos/administração & dosagem , Animais , Cálcio/metabolismo , Bloqueadores dos Canais de Cálcio/administração & dosagem , Canais de Cálcio/genética , Canais de Cálcio/metabolismo , Morte Celular/efeitos dos fármacos , Humanos , Masculino , Doenças do Sistema Nervoso/genética , Doenças do Sistema Nervoso/metabolismo , Doenças do Sistema Nervoso/fisiopatologia , Neurônios/citologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Proteína Quinase C/genética , Proteína Quinase C/metabolismo , Ratos , Ratos Sprague-Dawley , Sinaptossomos/metabolismoRESUMO
The coronavirus disease 19 (COVID-19) pandemic is a significant psychological stressor in addition to its tremendous impact on every facet of individuals' lives and organizations in virtually all social and economic sectors worldwide. Fear of illness and uncertainty about the future precipitate anxiety- and stress-related disorders, and several groups have rightfully called for the creation and dissemination of robust mental health screening and treatment programs for the general public and front-line healthcare workers. However, in addition to pandemic-associated psychological distress, the direct effects of the virus itself (several acute respiratory syndrome coronavirus; SARS-CoV-2), and the subsequent host immunologic response, on the human central nervous system (CNS) and related outcomes are unknown. We discuss currently available evidence of COVID-19 related neuropsychiatric sequelae while drawing parallels to past viral pandemic-related outcomes. Past pandemics have demonstrated that diverse types of neuropsychiatric symptoms, such as encephalopathy, mood changes, psychosis, neuromuscular dysfunction, or demyelinating processes, may accompany acute viral infection, or may follow infection by weeks, months, or longer in recovered patients. The potential mechanisms are also discussed, including viral and immunological underpinnings. Therefore, prospective neuropsychiatric monitoring of individuals exposed to SARS-CoV-2 at various points in the life course, as well as their neuroimmune status, are needed to fully understand the long-term impact of COVID-19, and to establish a framework for integrating psychoneuroimmunology into epidemiologic studies of pandemics.
Assuntos
Infecções por Coronavirus/psicologia , Síndrome da Liberação de Citocina/psicologia , Transtornos Mentais/psicologia , Doenças do Sistema Nervoso/psicologia , Pneumonia Viral/psicologia , Doença Aguda , Ansiedade/etiologia , Ansiedade/imunologia , Ansiedade/psicologia , Translocação Bacteriana , Betacoronavirus , COVID-19 , Doença Crônica , Infecções por Coronavirus/complicações , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/terapia , Doenças Desmielinizantes/etiologia , Doenças Desmielinizantes/imunologia , Doenças Desmielinizantes/fisiopatologia , Doenças Desmielinizantes/psicologia , Depressão/etiologia , Depressão/imunologia , Depressão/psicologia , Humanos , Fatores Imunológicos/efeitos adversos , Transtornos Mentais/etiologia , Transtornos Mentais/imunologia , Saúde Mental , Doenças do Sistema Nervoso/etiologia , Doenças do Sistema Nervoso/imunologia , Doenças do Sistema Nervoso/fisiopatologia , Doenças Neurodegenerativas/etiologia , Doenças Neurodegenerativas/imunologia , Doenças Neurodegenerativas/fisiopatologia , Doenças Neurodegenerativas/psicologia , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/imunologia , Pneumonia Viral/terapia , Psiconeuroimunologia , Transtornos Psicóticos/etiologia , Transtornos Psicóticos/imunologia , Transtornos Psicóticos/psicologia , Saúde Pública , SARS-CoV-2 , Transtornos de Estresse Pós-Traumáticos/etiologia , Transtornos de Estresse Pós-Traumáticos/imunologia , Transtornos de Estresse Pós-Traumáticos/psicologiaRESUMO
BACKGROUND: Xingnaojing injection (XNJi) is widely used for acute cerebral hemorrhage. However, the efficacy of XNJi for acute cerebral hemorrhage has not been comprehensively proved by systematic analysis yet. Therefore, it is essential to evaluate the efficacy and safety of XNJi in an evidence-based method. METHODS: Six databases were searched with XNJi used for acute cerebral hemorrhage in randomized controlled trials (RCTs). Meta-analysis was performed by Review Manager 5.3. The efficacy rate, brain edema, cerebral hematoma, neurological deficit score, hs-crp, Glasgow Coma Scale (GCS), and activities of daily living (ADL) were systematically evaluated. The Cochrane risk of bias was used to evaluate the methodological quality of eligible studies. RESULTS: This study is registered with PROSPERO (CRD42018098737). Twenty-nine studies with a total of 2638 patients were included in this meta-analysis. Compared with conventional treatment, XNJi got higher efficacy rate (ORâ=â3.37, 95% CI [2.65, 4.28], Pâ<â.00001). Moreover, XNJi showed significant enhancement of efficacy rate via subgroup analysis in course and dosage. In addition, XNJi demonstrated significant improvement in Chinese stroke scale (CSS) and National Institutes of Health Stroke Scale (NHISS) (mean difference [MD]â=â-4.74, 95% CI [-5.89, -3.60], Pâ<â.00001; MDâ=â-4.45, 95% CI [-5.49, -3.41], Pâ<â.00001), GCS (MDâ=â2.72, 95% CI [2.09, 3.35], Pâ<â.00001). It also remarkably decreased the level of hs-crp (MDâ=â-6.50, 95% CI [-7.79, -5.21], Pâ<â.00001), enhanced ADL (MDâ=â20.38, 95% CI [17.98, 22.79], Pâ<â.00001), and alleviated hematoma and edema (MDâ=â-2.53, 95% CI [-4.75, -0.31] Pâ<â.05; MDâ=â-1.74 95% CI [-2.42, -1.07] Pâ<â.00001) compared with conventional treatment. CONCLUSION: XNJi is effective in treating acute cerebral hemorrhage with significant improvement of CSS, NHISS and impairment of hs-crp, hematoma, and edema compared with conventional treatment. Moreover, XNJi got remarkable efficacy at the dose of 20, 30, 60âmL and from 7 to 28 days. No serious adverse reactions occurred. These results were mainly based on small-sample and low-quality studies. Therefore, more rigorous, large-scale RCTs were further needed to confirm its efficacy, safety, and detailed characteristic of application.
Assuntos
Hemorragia Cerebral/tratamento farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Atividades Cotidianas , Doença Aguda , Adulto , Idoso , Idoso de 80 Anos ou mais , Edema Encefálico/epidemiologia , Proteína C-Reativa/análise , Proteína C-Reativa/efeitos dos fármacos , Hemorragia Cerebral/epidemiologia , Medicamentos de Ervas Chinesas/efeitos adversos , Medicamentos de Ervas Chinesas/uso terapêutico , Feminino , Escala de Coma de Glasgow/estatística & dados numéricos , Hematoma , Humanos , Injeções , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/epidemiologia , Doenças do Sistema Nervoso/fisiopatologia , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
AIM: Carbon monoxide (CO) is a colorless, odorless gas and tasteless. CO poisoning (COP) is one of the most frequently encountered inhalation poisonings. The most common cause of morbidity in COP is delayed neurological sequelae (DNS). DNS is the occurrence of neuropsychiatric findings within 2-240â¯days after discharge of patients with COP and there are no definitive diagnostic criteria. The aim of our study is; to determine the risk factors and incidence of DNS. METHOD: Our study is a retrospective, observational study. Patients with the diagnosis of COP in the emergency department between 2015 and 2016 were included in the study. Patients age, gender, findings in the initial physical examination (PE) and neurological examination (NE), blood carboxyhemoglobin (COHb) level, relation between hyperbaric oxygen (HBO) treatment and DNS were assessed. RESULTS: Total of 72 patients were included in the study. Mean age was 33.43⯱â¯20.89. It was determined that pathological findings in the initial NE are a significant predictive factor for DNS (Odds ratio 18.600, p:0.004). Significant relation between NE and HBO treatment was present (p:00.1). There was no statistically significant relationship between initial COHb level and receiving HBO treatment (p:0.9). Median COHb level of patients with DNS was 30 (min:10, max: 43), median COHb level of patients without DNS was 25 (min:10, max:44) and there was no statistically significant relationship between the two groups according to COHb levels (p:0.7). CONCLUSION: Pathological findings in the initial neurological examination had a predictive value for delayed neurological sequelae in patients with carbon monoxide poisoning.
Assuntos
Intoxicação por Monóxido de Carbono/fisiopatologia , Carboxihemoglobina/metabolismo , Doenças do Sistema Nervoso/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Atenção , Intoxicação por Monóxido de Carbono/metabolismo , Intoxicação por Monóxido de Carbono/psicologia , Intoxicação por Monóxido de Carbono/terapia , Criança , Pré-Escolar , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/psicologia , Confusão/epidemiologia , Confusão/etiologia , Confusão/fisiopatologia , Confusão/psicologia , Feminino , Hospitalização , Humanos , Oxigenoterapia Hiperbárica/estatística & dados numéricos , Hiperfagia/epidemiologia , Hiperfagia/etiologia , Hiperfagia/fisiopatologia , Hiperfagia/psicologia , Lactente , Tempo de Internação , Masculino , Transtornos da Memória/epidemiologia , Transtornos da Memória/etiologia , Transtornos da Memória/fisiopatologia , Transtornos da Memória/psicologia , Pessoa de Meia-Idade , Rigidez Muscular/epidemiologia , Rigidez Muscular/etiologia , Rigidez Muscular/fisiopatologia , Rigidez Muscular/psicologia , Doenças do Sistema Nervoso/etiologia , Doenças do Sistema Nervoso/fisiopatologia , Doenças do Sistema Nervoso/psicologia , Exame Neurológico , Exame Físico , Equilíbrio Postural , Fatores de Risco , Transtornos de Sensação/epidemiologia , Transtornos de Sensação/etiologia , Transtornos de Sensação/fisiopatologia , Transtornos de Sensação/psicologia , Fatores de TempoRESUMO
Pain is a complex physiological process that includes many components. Growing evidence supports the idea that oxidative stress and Ca2+ signaling pathways participate in pain detection by neurons. The main source of endogenous reactive oxygen species (ROS) is mitochondrial dysfunction induced by membrane depolarization, which is in turn caused by Ca2+ influx into the cytosol of neurons. ROS are controlled by antioxidants, including selenium. Selenium plays an important role in the nervous system, including the brain, where it acts as a cofactor for glutathione peroxidase and is incorporated into selenoproteins involved in antioxidant defenses. It has neuroprotective effects through modulation of excessive ROS production, inflammation, and Ca2+ overload in several diseases, including inflammatory pain, hypersensitivity, allodynia, diabetic neuropathic pain, and nociceptive pain. Ca2+ entry across membranes is mediated by different channels, including transient receptor potential (TRP) channels, some of which (e.g., TRPA1, TRPM2, TRPV1, and TRPV4) can be activated by oxidative stress and have a role in the induction of peripheral pain. The results of recent studies indicate the modulator roles of selenium in peripheral pain through inhibition of TRP channels in the dorsal root ganglia of experimental animals. This review summarizes the protective role of selenium in TRP channel regulation, Ca2+ signaling, apoptosis, and mitochondrial oxidative stress in peripheral pain induction.
Assuntos
Doenças do Sistema Nervoso/fisiopatologia , Selênio/fisiologia , Animais , Sinalização do Cálcio , Humanos , Neuralgia/fisiopatologia , Canais de Potencial de Receptor Transitório/metabolismoRESUMO
Vitamin D3 is among the major neurosteroids whose role in developing and adult brain is intensively studied now. Its active form 1,25(OH)2D3 regulates the expression and functioning of a range of brain-specific proteins, which orchestrate the neurotransmitter turnover, neurogenesis and neuroplasticity. Despite numerous studies of the vitamin D role in normal and pathological brain function, there is little evidence on the mechanisms of alterations in excitatory and inhibitory neurotransmission under vitamin D deficiency (VDD). Using the animal model we characterized the dysfunction of excitatory and inhibitory neurotransmission under alimentary VDD. The shift between unstimulated and evoked GABA release under VDD was largely reversed after treatment of VDD, whereas the impairments in glutamatergic system were only partially recovered after 1-month vitamin D3 supplementation. The increase of the external glutamate level and unstimulated GABA release in brain nerve terminals was associated with intensified ROS production and higher [Ca2+]i in presynapse. The negative allosteric modulation of presynaptic mGlu7 receptors significantly enhanced exocytotic GABA release, which was decreased under VDD, thereby suggesting the neuroprotective effect of such modulation of inhibitory neurotransmission. Synaptic plasma membranes and cytosolic proteins contribute to the decreased stimulated release of neurotransmitter, by being the crucial components, whose functional state is impaired under VDD. The critical changes with synaptic vesicles occurred at the docking step of the process, whereas malfunctioning of synaptic cytosolic proteins impacted the fusion event foremost. The decreased amplitude of exocytosis was inherent for non-excitable cells as well, as evidenced by lower platelet degranulation. Our data suggest the presynaptic dysfunction and proinflammatory shift as the early events in the pathogenesis of VDD-associated disorders and provide evidences for the neuroprotective role of vitamin D3.
Assuntos
Encéfalo/fisiopatologia , Colecalciferol/deficiência , Inflamação/fisiopatologia , Doenças do Sistema Nervoso/metabolismo , Sinapses/patologia , Deficiência de Vitamina D/fisiopatologia , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Colecalciferol/metabolismo , Colecalciferol/farmacologia , Colesterol/metabolismo , Modelos Animais de Doenças , Ácido Glutâmico/metabolismo , Inflamação/metabolismo , Inflamação/patologia , Masculino , Fusão de Membrana , Camundongos Endogâmicos C57BL , Doenças do Sistema Nervoso/fisiopatologia , Vias Neurais , Fosfolipídeos/metabolismo , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Receptores de Glutamato Metabotrópico/metabolismo , Sinapses/metabolismo , Deficiência de Vitamina D/metabolismo , Vitaminas/farmacologia , Ácido gama-Aminobutírico/metabolismoRESUMO
PURPOSE OF REVIEW: In the last three decades, the use of eye movements and vestibular testing in many neurological disorders has accelerated, primarily because of practical technologic developments. Although the acute vestibular syndrome is a prime example of this progress, more chronic neurologic and systemic disorders have received less attention. We focus here on recent contributions relating vestibular and ocular motor abnormalities in inflammatory, demyelinating, metabolic, and peripheral nervous system disorders RECENT FINDINGS: Vestibular abnormalities have been identified in acute demyelinating neuropathies (AIDP), in novel genetic mutations responsible for CANVAS (cerebellar ataxia, neuropathy vestibular areflexia syndrome), and in other inherited neuropathies (variants of Charcot-Marie-Tooth disease). In addition, there are differentiating characteristics between the most common CNS demyelinating disorders: multiple sclerosis and neuromyelitis optica (NMO). We summarize new information on Vitamin D metabolism in benign paroxysmal positional vertigo (BPPV), followed by a brief review of the vestibular and ocular motor findings in Wernicke's encephalopathy. We conclude with findings in several paraneoplastic/autoimmune disorders. SUMMARY: This literature review highlights the impact of a careful vestibular and ocular motor evaluation in common neurologic disorder, not only for the initial diagnosis but also for monitoring disease and rehabilitation. A careful examination of eye movements and vestibular function, supplemented with new video techniques to quantify the findings, should be part of the standard neurologic examination.
Assuntos
Doenças Autoimunes/diagnóstico , Doenças Desmielinizantes/diagnóstico , Movimentos Oculares/fisiologia , Doenças Metabólicas/diagnóstico , Exame Neurológico , Doenças Autoimunes/fisiopatologia , Doenças Desmielinizantes/fisiopatologia , Humanos , Doenças Metabólicas/fisiopatologia , Doenças do Sistema Nervoso/fisiopatologia , Testes de Função VestibularRESUMO
The purpose of the present study was to investigate the effects of transcranial direct current stimulation (tDCS) on motor recovery in adult patients with stroke, taking into account the parameters that could influence the motor recovery responses. The second aim was to identify the best tDCS parameters and recommendations available based on the enhanced motor recovery demonstrated by the analyzed studies. Our systematic review was performed by searching full-text articles published before February 18, 2019 in the PubMed database. Different methods of applying tDCS in association with several complementary therapies were identified. Studies investigating the motor recovery effects of tDCS in adult patients with stroke were considered. Studies investigating different neurologic conditions and psychiatric disorders or those not meeting our methodologic criteria were excluded. The main parameters and outcomes of tDCS treatments are reported. There is not a robust concordance among the study outcomes with regard to the enhancement of motor recovery associated with the clinical application of tDCS. This is mainly due to the heterogeneity of clinical data, tDCS approaches, combined interventions, and outcome measurements. tDCS could be an effective approach to promote adaptive plasticity in the stroke population with significant positive premotor and postmotor rehabilitation effects. Future studies with larger sample sizes and high-quality studies with a better standardization of stimulation protocols are needed to improve the study quality, further corroborate our results, and identify the optimal tDCS protocols.
Assuntos
Córtex Motor/fisiopatologia , Recuperação de Função Fisiológica/fisiologia , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral/fisiopatologia , Estimulação Transcraniana por Corrente Contínua , Humanos , Córtex Motor/fisiologia , Doenças do Sistema Nervoso/complicações , Doenças do Sistema Nervoso/fisiopatologia , Doenças do Sistema Nervoso/reabilitação , Acidente Vascular Cerebral/complicações , Reabilitação do Acidente Vascular Cerebral/métodos , Estimulação Transcraniana por Corrente Contínua/métodosRESUMO
Involuntary attention allows for the detection and processing of novel and potentially relevant stimuli that lie outside of cognitive focus. These processes comprise change detection in sensory contexts, automatic orientation toward this change, and the selection of adaptive responses, including reorientation to the original goal in cases when the detected change is not relevant for task demands. These processes have been studied using the Event-Related Potential (ERP) technique and have been associated to the Mismatch Negativity (MMN), the P3a, and the Reorienting Negativity (RON) electrophysiological components, respectively. This has allowed for the objective evaluation of the impact of different neuropsychiatric pathologies on involuntary attention. Additionally, these ERP have been proposed as alternative measures for the early detection of disease and the tracking of its progression. The objective of this review was to integrate the results reported to date about MMN, P3a, and RON in different neurological and psychiatric disorders. We included experimental studies with clinical populations that reported at least two of these three components in the same experimental paradigm. Overall, involuntary attention seems to reflect the state of cognitive integrity in different pathologies in adults. However, if the main goal for these ERP is to consider them as biomarkers, more research about their pathophysiological specificity in each disorder is needed, as well as improvement in the general experimental conditions under which these components are elicited. Nevertheless, these ERP represent a valuable neurophysiological tool for early detection and follow-up of diverse clinical populations.