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The etiology of central nervous system(CNS)diseases is complex and mostly unknown,and patients are often left with sequelae and poor prognosis.Recently,ferroptosis has emerged as a unique oxidative stress-induced cell death pathway and is important in various CNS diseases.It is an important mode of neuronal cell death.This article summarizes the molecular mechanism of ferroptosis,research progress of ferroptosis in CNS diseases,and application of ferroptosis inhibitors in CNS diseases to provide new targets and clini-cal references for CNS disease treatment.
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Circular RNA(circRNA)is an emerging class of endogenous non-coding RNA,which is widely expressed in the brain and plays an important role in a variety of biological processes.Research has shown that circRNA plays a key role in physiological and pathological processes of the brain,such as neurodevelopment,synaptic plasticity and neurodegenerative diseases through a variety of mecha-nisms such as adsorption of microRNA,binding to proteins and translation of peptides.In the field of drug addiction,the expression of circRNA is significantly changed in animal models and brains of addicts,and the regulation involves neural adaptation in brain regions that form the reward circuit such as the nucleus accumbens and prefrontal cortex.Additionally,addiction-related circRNAs are closely associated with neurotransmitter systems,signaling pathways,and neuroinflammatory responses,and they influ-ence the formation and maintenance of drug addiction by modulating gene expression networks related to drug addiction.Here,the biogenesis and regulatory mechanism of circRNA as well as its important role in brain function and drug addiction are reviewed in order to provide a new perspective for explora-tions of the pathological mechanism of drug addiction.
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Corneal confocal microscopy (CCM) is a non-invasive, simple and rapid visual corneal imaging technique, which can directly conduct real-time collection and quantitative analysis of corneal nerve fibers. Studies have shown that CCM can be used in the diagnosis and prognosis evaluation of degenerative diseases, demyelinating diseases, degenerative diseases and other types of diseases of the central nervous system. In this paper, the recent advance in CCM in neurological diseases is summarized to provide new ideas for their diagnosis and prognosis evaluation.
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Hevin is one of the extracellular matrix proteins secreted by astrocytes. Under physiological conditions, Hevin plays an important role in synaptogenesis in the central nervous system (CNS); secreted protein, acidic and rich in cysteine (SPARC) is its homologue and antagonizes the synaptogenic effects of Hevin. In pathological conditions, the expressions of Hevin and SPARC are altered, suggesting their possible roles at synaptic reorganization in various disease process, such as brain injury, Alzheimer's disease, epilepsy and brain tumors; however, the specific mechanism is not totally understood yet. So this paper reviews the mechanism of Hevin/SPARC in CNS synaptogenesis, reorganization and diseases to provide ideas for further research.
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Nicotinamide mononucleotide (NMN) is an important precursor in conversing nicotinamide adenine dinucleotide (NAD +) in the body. By elevating NAD + level in the body, NMN enhances the hydrogen transfer function of NAD + in biological processes, promotes the synthesis of proteins and polysaccharides, improves substance transportation and regulatory efficiency, and enhances metabolic functions. Specifically, in central nervous system disease, NMN exerts neuroprotective effect through antioxidation, anti-inflammation, mitochondrial protection, and prevention of neuronal and axonal degeneration. This review focuses on the therapeutic role of NMN in common central nervous system diseases and their neuroprotective mechanisms, so as to further understand the role of NMN in central nervous system diseases, and provide references for predicting therapeutic targets and screening therapeutic drugs for central nervous system diseases.
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As an essential trace element in living organisms, copper is actively involved in normal physiological processes in various systems and is maintained at low level to achieve copper homeostasis. Copper homeostasis, once being disrupted, would induce cell death, and this new form of cell death is known as copper death. In recent years, copper death has been increasingly recognized as an important factor mediating the onset and progression of central nervous system (CNS) diseases. Therefore, we review the pathogenic mechanism of copper death in CNS diseases, as well as its therapeutic strategies so as to deepen the understanding of researchers.
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Iron is an essential metal element for human body. It is involved in many important biological metabolic processes. Iron metabolism in the central nervous system has a strict regulatory mechanism. Iron deposition occurs when the homeostasis of iron metabolism is disrupted, leading to an increase in neuronal iron uptake and a decrease in iron discharge. Aging cells develop specific iron deposition, and excessive iron produce reactive oxygen species, which can damage DNA. Highly reactive aldehydes result in irreversible modification of proteins. Stored proteins were stimulated to release iron, which in turn produces more reactive oxygen species, ultimately leading to iron-mediated cell death and neurological dysfunction. The widely used methods for assessing iron deposition include susceptibility weighted imaging and quantitative susceptibility mapping. Abnormally elevated brain iron deposition has been observed in a variety of central nervous system diseases, especially in Parkinson disease. Iron deposition plays an important role in early diagnosis, differential diagnosis, disease evaluation and monitoring and therapeutic effect evaluation of Parkinson disease. This article reviews the research progress of iron deposition in Parkinson disease.
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Brain delivery of drugs remains challenging due to the presence of the blood-brain barrier (BBB). With advances in nanotechnology and biotechnology, new possibilities for brain-targeted drug delivery have emerged. Biomimetic nano drug delivery systems with high brain-targeting and BBB-penetrating capabilities, along with good biocompatibility and safety, can enable 'invisible' drug delivery. In this review, five different types of biomimetic strategies are presented and their research progress in central nervous system disorders is reviewed. Finally, the challenges and future prospects for biomimetic nano drug delivery systems in intracerebral drug delivery are summarized.
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Pericytes are a kind of microvascular parietal cells, which constitute neurovascular units together with neurons, astrocytes, microglia, vascular endothelial cells and vascular smooth muscle cells to maintain the basic function of the brain. Pericyte dysfunction can lead to cerebral microcirculation dysfunction, which is related to the occurrence and development of a variety of nervous system diseases. This article reviews the characteristics, identification and subtypes of pericytes, their relations with cerebral microcirculation, and their correlation with central nervous system diseases.
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The treatment of central nervous system diseases has always been a hot topic,owning to its complexity and existence of blood-brain barrier.In recent years,studies on mesenchymal stem cells-derived exosomes (MSCs-EVS) showed that MSCs-EVS are not only potential therapeutic drugs for central nervous system diseases,but also natural carriers of therapeutic drugs due to their good biocompatibility and ability to cross the blood-brain barrier.This paper reviews the application and underling mechanism of MSCs-EVS in treatment of central nervous system diseases,and looks forward to its applications in central nervous system disease.
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Regulatory noncoding RNA (ncRNA), mainly including long noncoding RNA (lncRNA), microRNA (miRNA) and circular RNA (circRNA), is one of the research hotspots at home and abroad in recent years. Numerous studies have shown that LncRNA, miRNA and circRNA are significantly differentially expressed and play an important role in central nervous system diseases, which may become the potential targets for novel diagnostic markers and for the treatment of diseases. In this paper, the differential expression, possible mechanism and the latest research progress of lncRNA, miRNA and circRNA in central nervous system diseases are reviewed in order to provide reference for further research.
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Abstract Naegleria fowleri is a free-living amoeba commonly found in the environment, mainly in fresh water and soil. This protozoon is occasionally involved in cases of fatal central nervous system disease in humans and other animal species. We describe here a case of meningoencephalitis due to Naegleria fowleri in cattle, in southern Brazil. A four-year-old Angus cow presented a clinical history of initial mild neurological signs that progressed to paddling movements, opisthotonus and lateral recumbency after five days. This animal had been kept in an irrigated rice stubble paddock. Grossly, the main lesions consisted of multiple areas of malacia in the right olfactory bulb, piriform lobes, hippocampus, frontal lobe cortex and fornix, along with severe thickening of the mesencephalon and rhombencephalon leptomeninges. Microscopically, severe multifocal necrosuppurative and hemorrhagic meningoencephalitis associated with a large quantity of amoebic trophozoites was present. The latter were confirmed to be Naegleria spp., through immunohistochemistry. Based on the strong congruence with the histopathological data of known cases reported in the literature, a probable association with Naegleria fowleri was established. To our knowledge, this is only the second report of Naegleria fowleri-associated meningoencephalitis in cattle in South America, and it is the first in southern Brazil.
Resumo Naegleria fowleri é uma ameba de vida livre, comumente encontrada no meio ambiente, principalmente em água doce e no solo. Este protozoário é ocasionalmente associado a casos fatais de doença do sistema nervoso central em seres humanos e espécies animais. No presente trabalho, um caso de meningoencefalite por Naegleria fowleri em um bovino na região sul do Brasil é descrito. Uma vaca Angus, de quatro anos de idade apresentou histórico clínico caracterizado inicialmente por sinais neurológicos leves que progrediram para movimentos de pedalagem, opistótono e decúbito lateral após cinco dias. Este animal era mantido em um piquete em resteva de arroz irrigado. Macroscopicamente, as principais lesões foram caracterizadas por múltiplas áreas de malacia no bulbo olfatório direito, lobos piriformes, hipocampo, córtex do lobo frontal e no fórnix, bem como acentuado espessamento das leptomeninges do mesencéfalo e rombencéfalo. Microscopicamente, meningoencefalite necrossupurativa e hemorrágica associada à grande número de trofozoítos amebianos foram observadas. Estes foram confirmados como Naegleria spp. através de imuno-histoquímica. Baseado na forte congruência apresentada entre os dados histopatológicos provenientes de casos conhecidos publicados na literatura, uma provável associação com Naegleria fowleri foi estabelecida. O presente trabalho trata-se do segundo relato de meningoencefalite associada à Naegleria fowleri em bovinos na América do Sul e o primeiro na região sul do Brasil.
Subject(s)
Animals , Cattle , Cattle Diseases/parasitology , Naegleria fowleri/isolation & purification , Central Nervous System Protozoal Infections/veterinary , Central Nervous System Protozoal Infections/parasitologyABSTRACT
Astrocytes exist in the central nervous system widely,through cell-cell communication in neurovascular units,playing an important role in providing metabolic support for neurons,regulating nerve function and plasticity and so on.There is evidence that exosomes play a key regulatory role in intercellular communication by carrying natural cargo molecules and participate in a variety of pathophysiological processes.However,the role of astrocyte-derived exosome in central nervous system diseases is largely unknown.In this paper,the classification,characteristics,biomarkers,physiological functions,functions of astrocyte-derived exosome and their roles in central nervous system diseases are reviewed,for a deeper understanding of the role of astrocytes in central nervous system diseases.
ABSTRACT
Astrocytes exist in the central nervous system widely, through cell-cell communication in neurovascular units, playing an important role in providing metabolic support for neurons, regulating nerve function and plasticity and so on.There is evidence that exosomes play a key regulatory role in intercellular communication by carrying natural cargo molecules and participate in a variety of pathophysiological processes.However, the role of astrocyte-derived exosome in central nervous system diseases is largely unknown.In this paper, the classification, characteristics, biomarkers, physiological functions, functions of astrocyte-derived exosome and their roles in central nervous system diseases are reviewed, for a deeper understanding of the role of astrocytes in central nervous system diseases.
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Este estudo teve o objetivo de determinar a frequência das enfermidades do sistema nervoso central que afetam bezerros até 12 meses de idade na região sul do Rio Grande do Sul. Foi realizado um estudo retrospectivo estabelecendo-se as principais enfermidades observadas nesta categoria de bovinos em um período de 36 anos. Foram revisados os protocolos de necropsia e de materiais remetidos ao Laboratório Regional de Diagnóstico da Faculdade de Veterinária da Universidade Federal de Pelotas entre janeiro de 1978 e dezembro de 2015 referentes aos bovinos até 12 meses de idade que apresentavam sinais neurológicos. Foram resgatados os dados epidemiológicos referentes à procedência dos animais, tipo de criação, raça, idade e época de ocorrência e frequência de cada enfermidade. Foram identificados 615 casos de bovinos com sinais neurológicos, dos quais 162 (26,3%) tinham até 12 meses de idade. Os diagnósticos foram agrupados por etiologia, sendo que as enfermidades virais totalizaram 42,6% dos casos; as doenças bacterianas 19,1% e as doenças parasitárias 17,3%. Os defeitos congênitos e as doenças hereditárias representaram 6,2% dos casos, seguidos pelas intoxicações e micotoxicoses com 4,9%; pelas doenças carenciais e multifatoriais ambas com 2,5% dos casos e pelos traumatismos com 1,9%, doenças degenerativas e neoplasias com 0,6% dos diagnósticos. Os casos inconclusivos representaram 1,86% do total. Nos bezerros até os 90 dias as principais enfermidades foram os defeitos congênitos e as meningites e encefalites por causas bacterianas, além dos abscessos do sistema nervoso central; nos bezerros entre os quatro e nove meses as enfermidades tiveram uma frequência mais baixa destacando-se apenas a raiva. A partir dos 10 até os 12 meses a babesiose, a raiva e a encefalite por herpesvírus bovino foram as mais importantes como causa de morte.(AU)
This paper aimed to determine the frequency of diseases of the central nervous system affecting calves under 12 months of age in southern Rio Grande do Sul. A retrospective study was conducted determining the main diseases observed in this category of cattle over a period of 36 years. We reviewed all the necropsy protocols and materials sent to the laboratory between 1978 and December 2015 relating to cattle under 12 months of age that showed neurological signs. The epidemiological data concerning the origin of the animals, raising system, breed, age and time of occurrence of each disease and frequency were taken from necropsy protocols. Out of 615 cases with neurological signs, 162 (26.3%) corresponded to cattle with age up to 12 months. The diagnoses were grouped by etiology of viral diseases (42.6%), bacterial diseases (19.1%), parasitic diseases (17.3%), congenital defects, hereditary diseases (6.2%), poisoning, mycotoxicoses (4.9%), nutritional deficiency and multifactorial diseases (2.5%), and trauma, degenerative diseases and neoplasms with 0.62% of diagnoses. Inconclusive cases represented 1.9% of the total diagnosed. In 1 to 90 day-old calves the main diseases observed were congenital defects, meningitis and encephalitis caused by bacteria. Central nervous system abscesses were also observed. In 4 to 9 month-old calves a lower frequency of disease were noted. Rabies was the most important disease diagnosed in this category. Babesiosis, rabies and encephalitis by bovine herpesvirus were the most important causes of death in 10 to 12 month-old calves.(AU)
Subject(s)
Guinea Pigs , Cattle/abnormalities , Central Nervous System Diseases/veterinaryABSTRACT
@# Intestinal flora plays an important role in the process of human health and disease conversion. It not only participates in a number of physiological processes in the host, but also affects the central nervous system (CNS) -related diseases, which may involve in neurotransmitter, immune, endocrine, metabolites, etc. Intestinal dysbacteriosis plays a role in the development of CNS diseases, such as ischemic brain injury, Parkinson's disease, Alzheimer's disease, multiple sclerosis, hepatic encephalopathy, and mental disorders, etc. Fecal microbes transplantation, exercise training, acupuncture and Tuina therapy can improve the intestinal flora balance, which may be potential for the treatment and prevention of some nervous system diseases.
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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.
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The endocannabinoid system has wide-ranged effect on human sleep,pain,mood,metabolism,and neurodevelopment.As one of the members of this system,cannabinoid receptor 1 plays an important protective effect on some neurodegenerative diseases,such as multiple sclerosis disease,Huntington's disease,and Alzheimer's disease.This article aims to outline the protective mechanism of endocannabinoid system and cannabinoid receptor 1 in neurodegenerative diseases.
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The intestinal flora in the human intestinal tract plays an important role in regulating the intestinal function and maintaining the homeostasis of intestinal state. An increasing number of basic experimental studies have found that intestinal flora can communicate with brain through gut-brain axis (GBA). GBA refers to the neurohumoral network of two-way communication between the intestinal tract and the brain, including immunity, vagus nerve, endocrine, and neurotransmitter. In addition, a large number of studies have suggested that the disorder or absence of intestinal flora may lead to many central nervous system diseases, such as multiple sclerosis, Alzheimer's disease, Parkinson's disease, autism spectrum disorder, and hepatic encephalopathy. This article reviews the research progress of the interaction between intestinal flora and brain function to provide theoretical support for further researches on intestinal flora and brain, as well as the treatment strategies of related central nervous system diseases.
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As a new model animal, zebrafish has been widely used in the research of the development and disease related to various organs, such as nervous, cardiovascular, digestive and hemopoietic system. Central nervous system ( CNS) disease is one of the leading causes of death and disability worldwide. There is still lacking of effective therapeutic strategies to treat most of the CNS diseases, due to the low ability of self-regeneration and recovery of the neurons after injury. In recent years, zebrafish has been proved to be an ideal vertebrate model to study some of the CNS diseases because their genetic physiology and other features are closed and similar to humans. The application of zebrafish in CNS diseases has contributed largely on understanding the mechanisms and on the therapy of CNS diseases. This review summarizes the recent progress of the applications of zebrafish on the study of CNS diseases.