Pub Date : 2020-05-16DOI: 10.20517/2347-8659.2019.22
V. Constantinides, G. Paraskevas, F. Boufidou, Maria Bourbouli, P. Paraskevas, L. Stefanis, E. Kapaki
Progressive supranuclear palsy, corticobasal degeneration, multiple system atrophy and dementia with Lewy bodies are the most common causes of atypical Parkinsonism and enter the differential diagnosis of Parkinson’s disease. multiple system atrophy, dementia with Lewy bodies and Parkinson’s disease are synucleinopathies, whereas progressive supranuclear palsy and corticobasal degeneration are tauopathies. Multiple cerebrospinal fluid markers have been applied on cohorts of patients with Parkinsonism, with the aim to develop biomarkers for these disorders. Total tau (τΤ), phosphorylated tau at threonine 181 (τP-181) and amyloid-beta with 42 amino acids (Aβ42) are considered classical biomarkers for Alzheimer’s disease. The aim of the present study is to review the literature regarding these classical cerebrospinal fluid biomarkers in cohorts with Parkinsonism, as well as present data on novel approaches regarding analysis of these proteins.
{"title":"Cerebrospinal fluid amyloid beta and tau proteins in atypical Parkinsonism: a review","authors":"V. Constantinides, G. Paraskevas, F. Boufidou, Maria Bourbouli, P. Paraskevas, L. Stefanis, E. Kapaki","doi":"10.20517/2347-8659.2019.22","DOIUrl":"https://doi.org/10.20517/2347-8659.2019.22","url":null,"abstract":"Progressive supranuclear palsy, corticobasal degeneration, multiple system atrophy and dementia with Lewy bodies are the most common causes of atypical Parkinsonism and enter the differential diagnosis of Parkinson’s disease. multiple system atrophy, dementia with Lewy bodies and Parkinson’s disease are synucleinopathies, whereas progressive supranuclear palsy and corticobasal degeneration are tauopathies. Multiple cerebrospinal fluid markers have been applied on cohorts of patients with Parkinsonism, with the aim to develop biomarkers for these disorders. Total tau (τΤ), phosphorylated tau at threonine 181 (τP-181) and amyloid-beta with 42 amino acids (Aβ42) are considered classical biomarkers for Alzheimer’s disease. The aim of the present study is to review the literature regarding these classical cerebrospinal fluid biomarkers in cohorts with Parkinsonism, as well as present data on novel approaches regarding analysis of these proteins.","PeriodicalId":19129,"journal":{"name":"Neuroimmunology and Neuroinflammation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42065610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-05-16DOI: 10.20517/2347-8659.2020.01
Ioanna Chalatsa, Katerina Melachroinou, Evangelia Emmanouilidou, K. Vekrellis
The discovery of diagnostic and prognostic biomarkers for neurodegenerative diseases represents an unmet clinical challenge. For example, the diagnosis of Parkinson’s disease (PD) relies mainly on the presence of clinical symptoms. Therefore, the identification and use of novel PD biomarkers would allow the application of diseasemodifying treatments at the very early stages of neurodegeneration. The presynaptic protein, α-synuclein, has been genetically and biochemically linked with PD pathogenesis and has been considered as a potential biomarker for the diagnosis of PD and the related synucleinopathies. The vast majority of studies have assessed the measurement of α-synuclein, alone or in combination with other biomarkers in the cerebrospinal fluid (CSF), since it is the biofluid that most closely reflects the pathophysiology of the brain. The diagnostic value of the monomeric α-synuclein but also the oligomeric, the phosphorylated and the aggregated forms of the protein has been evaluated using a variety of immunoassays. The results have so far been reproducible but the assays used are still lacking the required diagnostic accuracy. Recent reports have shown that Protein misfolding cyclic amplification is a technique that has the potential to detect α-synuclein seeds in samples of CSF with high sensitivity and across different synucleinopathies. In an effort to increase the source of biomarker for PD and related synucleinopathies, α-synuclein has also been measured in neuronal exosomes, small vesicles of endosomal origin that are secreted from neurons into the CSF or the periphery. The potential diagnostic value of exosomes stems from the notion that exosomes carry a disease-specific repertoire of marker proteins. Therefore, the assessment of exosomeassociated α-synuclein species may also open up new avenues for disease diagnosis in different synucleinopathies.
{"title":"Assessment of cerebrospinal fluid α-synuclein as a potential biomarker in Parkinson’s disease and synucleinopathies","authors":"Ioanna Chalatsa, Katerina Melachroinou, Evangelia Emmanouilidou, K. Vekrellis","doi":"10.20517/2347-8659.2020.01","DOIUrl":"https://doi.org/10.20517/2347-8659.2020.01","url":null,"abstract":"The discovery of diagnostic and prognostic biomarkers for neurodegenerative diseases represents an unmet clinical challenge. For example, the diagnosis of Parkinson’s disease (PD) relies mainly on the presence of clinical symptoms. Therefore, the identification and use of novel PD biomarkers would allow the application of diseasemodifying treatments at the very early stages of neurodegeneration. The presynaptic protein, α-synuclein, has been genetically and biochemically linked with PD pathogenesis and has been considered as a potential biomarker for the diagnosis of PD and the related synucleinopathies. The vast majority of studies have assessed the measurement of α-synuclein, alone or in combination with other biomarkers in the cerebrospinal fluid (CSF), since it is the biofluid that most closely reflects the pathophysiology of the brain. The diagnostic value of the monomeric α-synuclein but also the oligomeric, the phosphorylated and the aggregated forms of the protein has been evaluated using a variety of immunoassays. The results have so far been reproducible but the assays used are still lacking the required diagnostic accuracy. Recent reports have shown that Protein misfolding cyclic amplification is a technique that has the potential to detect α-synuclein seeds in samples of CSF with high sensitivity and across different synucleinopathies. In an effort to increase the source of biomarker for PD and related synucleinopathies, α-synuclein has also been measured in neuronal exosomes, small vesicles of endosomal origin that are secreted from neurons into the CSF or the periphery. The potential diagnostic value of exosomes stems from the notion that exosomes carry a disease-specific repertoire of marker proteins. Therefore, the assessment of exosomeassociated α-synuclein species may also open up new avenues for disease diagnosis in different synucleinopathies.","PeriodicalId":19129,"journal":{"name":"Neuroimmunology and Neuroinflammation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45105994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-05-11DOI: 10.20517/2347-8659.2019.018
Xinjie Zhang, Jianfeng Guo, Jun Yang
Idiopathic normal pressure hydrocephalus (iNPH) is characterized by abnormal cerebrospinal fluid (CSF) flow and consequent cerebral ventricular enlargement due to imbalance of CSF production and absorption. The typical triad symptoms, namely cognitive decline, gait disturbance, and urinary incontinence, are thought to be caused by disruption of CSF circulation. However, some patients may still experience symptomatic progression after functional shunting, suggesting that iNPH is far more complicated than a simple disorder of CSF circulation. Moreover, the diagnostic workup of iNPH can be challenging due to symptomatic and neuroimaging overlaps with other neurological disorders, such as Alzheimer’s disease. Furthermore, accumulating studies indicate that the pathogenesis of iNPH might relate to multiple mechanisms, including abnormalities of brain development, brain extracellular matrix, synaptic function, blood flow, and cerebral metabolism. Therefore, iNPH is not an isolated entity in occurrence and development. Nevertheless, different pathogeneses may result in protein content changes in CSF, and the biomarkers in CSF may reflect the possible mechanisms involving the etiology of iNPH and are potentially useful in assisting the diagnosis and treatment selection. In this review, we summarize the main findings of CSF biomarkers and aim to outline a possible synthetic profile in assisting iNPH diagnosis and therapeutic options.
{"title":"Cerebrospinal fluid biomarkers in idiopathic normal pressure hydrocephalus","authors":"Xinjie Zhang, Jianfeng Guo, Jun Yang","doi":"10.20517/2347-8659.2019.018","DOIUrl":"https://doi.org/10.20517/2347-8659.2019.018","url":null,"abstract":"Idiopathic normal pressure hydrocephalus (iNPH) is characterized by abnormal cerebrospinal fluid (CSF) flow and consequent cerebral ventricular enlargement due to imbalance of CSF production and absorption. The typical triad symptoms, namely cognitive decline, gait disturbance, and urinary incontinence, are thought to be caused by disruption of CSF circulation. However, some patients may still experience symptomatic progression after functional shunting, suggesting that iNPH is far more complicated than a simple disorder of CSF circulation. Moreover, the diagnostic workup of iNPH can be challenging due to symptomatic and neuroimaging overlaps with other neurological disorders, such as Alzheimer’s disease. Furthermore, accumulating studies indicate that the pathogenesis of iNPH might relate to multiple mechanisms, including abnormalities of brain development, brain extracellular matrix, synaptic function, blood flow, and cerebral metabolism. Therefore, iNPH is not an isolated entity in occurrence and development. Nevertheless, different pathogeneses may result in protein content changes in CSF, and the biomarkers in CSF may reflect the possible mechanisms involving the etiology of iNPH and are potentially useful in assisting the diagnosis and treatment selection. In this review, we summarize the main findings of CSF biomarkers and aim to outline a possible synthetic profile in assisting iNPH diagnosis and therapeutic options.","PeriodicalId":19129,"journal":{"name":"Neuroimmunology and Neuroinflammation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45715023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-05-11DOI: 10.20517/2347-8659.2019.14
Sri Jayanti, R. Moretti, C. Tiribelli, S. Gazzin
Inflammation links neurodegenerative, neuropsychiatric and other neurological diseases (NDs) with acute brain events. It is responsible for the alteration of neurotransmission and circuity, brain architecture, and cell fate, affecting mood and personality (anxiety, depression and schizophrenia) and behavior (decline in cognitive, motor and speech abilities, altered sleep, fatigue, pain sensitivity and dementia). Inflammation is also a key component in systemic chronic diseases (cardiovascular disease, cancer, diabetes, and metabolic syndrome), in which bilirubin has been demonstrated to improve the diseases by acting as a multi-target antiinflammatory molecule, and where the evaluation of pharmacological modulation of the pigment level as a therapeutic approach has already started. While altered serum bilirubin levels have been reported in ND patients, the potential activity of bilirubin in the brain is vague. This review summarizes the available fragmentary information on the interplay of bilirubin with neuroinflammation, aiming to elucidate the pigment’s role in the central nervous system environment.
{"title":"Bilirubin and inflammation in neurodegenerative and other neurological diseases","authors":"Sri Jayanti, R. Moretti, C. Tiribelli, S. Gazzin","doi":"10.20517/2347-8659.2019.14","DOIUrl":"https://doi.org/10.20517/2347-8659.2019.14","url":null,"abstract":"Inflammation links neurodegenerative, neuropsychiatric and other neurological diseases (NDs) with acute brain events. It is responsible for the alteration of neurotransmission and circuity, brain architecture, and cell fate, affecting mood and personality (anxiety, depression and schizophrenia) and behavior (decline in cognitive, motor and speech abilities, altered sleep, fatigue, pain sensitivity and dementia). Inflammation is also a key component in systemic chronic diseases (cardiovascular disease, cancer, diabetes, and metabolic syndrome), in which bilirubin has been demonstrated to improve the diseases by acting as a multi-target antiinflammatory molecule, and where the evaluation of pharmacological modulation of the pigment level as a therapeutic approach has already started. While altered serum bilirubin levels have been reported in ND patients, the potential activity of bilirubin in the brain is vague. This review summarizes the available fragmentary information on the interplay of bilirubin with neuroinflammation, aiming to elucidate the pigment’s role in the central nervous system environment.","PeriodicalId":19129,"journal":{"name":"Neuroimmunology and Neuroinflammation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47635192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-04-17DOI: 10.20517/2347-8659.2020.16
Sandra E. Muroy, G. Timblin, M. Preininger, Paulina Cedillo, K. Saijo
Aim: Excessive microglial inflammation has emerged as a key player in mediating the effects of aging and neurodegeneration on brain dysfunction. Thus, there is great interest in discovering transcriptional repressors that can control this process. We aimed to examine whether Phf15 one of the top differentially expressed genes in microglia during aging in humans could regulate transcription of proinflammatory mediators in microglia. Methods: Real-time quantitative PCR was used to assess Phf15 mRNA expression in mouse brain during aging. Lossof-function [short hairpin RNA (shRNA) -mediated knockdown (KD) and CRISPR/Cas9-mediated knockout (KO) of Phf15 ] and gain-of-function [retroviral overexpression (OE) of murine Phf15 cDNA] studies in a murine microglial cell line (SIM-A9) followed by immune activation with lipopolysaccharide were used to determine the effect of Phf15 on proinflammatory factor (Tnfα , IL-1β , and Nos2 ) mRNA expression. RNA sequencing was used to determine global transcriptional changes after Phf15 knockout under basal conditions and after lipopolysaccharide stimulation. Results: Phf15 expression increases in mouse brain during aging, similar to humans. KD, KO, and OE studies determined that Phf15 represses mRNA expression levels of proinflammatory mediators such as Tnfα , IL-1β , and Nos2 . Global transcriptional changes after Phf15 KO showed that Phf15 specifically represses genes related to the antiviral (type I interferon) response and cytokine production in microglia. Conclusion: We provide the first evidence that Phf15 is an important transcriptional repressor of microglial inflammation, regulating the antiviral response and proinflammatory cytokine production. Importantly, Phf15 regulates both basal and signal-dependent activation and controls the magnitude and duration of the microglial inflammatory response.
{"title":"Phf15 - a novel transcriptional repressor regulating inflammation in a mouse microglial cell line","authors":"Sandra E. Muroy, G. Timblin, M. Preininger, Paulina Cedillo, K. Saijo","doi":"10.20517/2347-8659.2020.16","DOIUrl":"https://doi.org/10.20517/2347-8659.2020.16","url":null,"abstract":"Aim: Excessive microglial inflammation has emerged as a key player in mediating the effects of aging and neurodegeneration on brain dysfunction. Thus, there is great interest in discovering transcriptional repressors that can control this process. We aimed to examine whether Phf15 one of the top differentially expressed genes in microglia during aging in humans could regulate transcription of proinflammatory mediators in microglia. Methods: Real-time quantitative PCR was used to assess Phf15 mRNA expression in mouse brain during aging. Lossof-function [short hairpin RNA (shRNA) -mediated knockdown (KD) and CRISPR/Cas9-mediated knockout (KO) of Phf15 ] and gain-of-function [retroviral overexpression (OE) of murine Phf15 cDNA] studies in a murine microglial cell line (SIM-A9) followed by immune activation with lipopolysaccharide were used to determine the effect of Phf15 on proinflammatory factor (Tnfα , IL-1β , and Nos2 ) mRNA expression. RNA sequencing was used to determine global transcriptional changes after Phf15 knockout under basal conditions and after lipopolysaccharide stimulation. Results: Phf15 expression increases in mouse brain during aging, similar to humans. KD, KO, and OE studies determined that Phf15 represses mRNA expression levels of proinflammatory mediators such as Tnfα , IL-1β , and Nos2 . Global transcriptional changes after Phf15 KO showed that Phf15 specifically represses genes related to the antiviral (type I interferon) response and cytokine production in microglia. Conclusion: We provide the first evidence that Phf15 is an important transcriptional repressor of microglial inflammation, regulating the antiviral response and proinflammatory cytokine production. Importantly, Phf15 regulates both basal and signal-dependent activation and controls the magnitude and duration of the microglial inflammatory response.","PeriodicalId":19129,"journal":{"name":"Neuroimmunology and Neuroinflammation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48656777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-04-10DOI: 10.20517/2347-8659.2020.04
Junya Tanaka
Resident microglia in the central nervous system (CNS) are activated rapidly in response to even minor pathologic changes in the CNS, releasing various cytokines, growth factors, reactive oxygen species and other bioactive substances, in addition to eliminating synapses and degenerating cells through phagocytosis. Monocytes in circulation invade the inflamed brain tissues and develop into macrophages that also produce several bioactive substances and engage in phagocytosis. This article introduces methods for distinguishing microglia and macrophages. The pathophysiological roles of resident microglia and macrophages are discussed in animal models with neuroinflammation in the brain either with or without disruption of the blood-brain barrier. Both cell types have ameliorating and aggravating effects on the pathologic CNS, and their different roles are addressed in this article. Furthermore, this article compares the effects of some pharmacological interventions to induce phenotypic cellular changes for improved outcomes of the pathologic CNS.
{"title":"Favorable and unfavorable roles of microglia and macrophages in the pathologic central nervous system","authors":"Junya Tanaka","doi":"10.20517/2347-8659.2020.04","DOIUrl":"https://doi.org/10.20517/2347-8659.2020.04","url":null,"abstract":"Resident microglia in the central nervous system (CNS) are activated rapidly in response to even minor pathologic changes in the CNS, releasing various cytokines, growth factors, reactive oxygen species and other bioactive substances, in addition to eliminating synapses and degenerating cells through phagocytosis. Monocytes in circulation invade the inflamed brain tissues and develop into macrophages that also produce several bioactive substances and engage in phagocytosis. This article introduces methods for distinguishing microglia and macrophages. The pathophysiological roles of resident microglia and macrophages are discussed in animal models with neuroinflammation in the brain either with or without disruption of the blood-brain barrier. Both cell types have ameliorating and aggravating effects on the pathologic CNS, and their different roles are addressed in this article. Furthermore, this article compares the effects of some pharmacological interventions to induce phenotypic cellular changes for improved outcomes of the pathologic CNS.","PeriodicalId":19129,"journal":{"name":"Neuroimmunology and Neuroinflammation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44844819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-03-21DOI: 10.20517/2347-8659.2019.31
Natalia Yanguas-Casás
Microglia are the resident immune cells in the brain and maintain homeostasis and functionality of this tissue. These cells are key producers of immune mediators, such as cytokines and chemokines, are critical for normal brain development, and affect neurogenesis, axonal migration, synapse formation and function, and programmed cell death, among others. Sex differences exist in many of these processes throughout brain development up to adulthood and the aged brain. In the last few years, sex differences in microglia responses, brain colonization, and number and morphology within the developing brain have drawn the attention of researchers as a potential explanation to the sex differences in the brain and due to their potential relevance in the incidence, prevalence, and outcome of many neurological disorders. In this review, we summarize the sex differences of microglial cell functions and their potential relevance in physiological as well as pathological conditions in the brain.
{"title":"Physiological sex differences in microglia and their relevance in neurological disorders","authors":"Natalia Yanguas-Casás","doi":"10.20517/2347-8659.2019.31","DOIUrl":"https://doi.org/10.20517/2347-8659.2019.31","url":null,"abstract":"Microglia are the resident immune cells in the brain and maintain homeostasis and functionality of this tissue. These cells are key producers of immune mediators, such as cytokines and chemokines, are critical for normal brain development, and affect neurogenesis, axonal migration, synapse formation and function, and programmed cell death, among others. Sex differences exist in many of these processes throughout brain development up to adulthood and the aged brain. In the last few years, sex differences in microglia responses, brain colonization, and number and morphology within the developing brain have drawn the attention of researchers as a potential explanation to the sex differences in the brain and due to their potential relevance in the incidence, prevalence, and outcome of many neurological disorders. In this review, we summarize the sex differences of microglial cell functions and their potential relevance in physiological as well as pathological conditions in the brain.","PeriodicalId":19129,"journal":{"name":"Neuroimmunology and Neuroinflammation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49195964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-03-21DOI: 10.20517/2347-8659.2019.009
L. Fracaro, B. Zoehler, C. Rebelatto
Spinal cord injury (SCI) is a serious clinical problem that affects approximately 17,500 new patients per year in the United States. The main causes of SCI are vehicle collisions, falls, violence (mainly gunshot wounds), and sports/recreational activities. The final severity of the damage results from primary and secondary mechanisms that begin at the time of injury and last for months after trauma. To reduce the extent of damage, several treatments have been proposed. This review summarizes results from several studies that have pointed to cell therapy as the main form of neuroregenerative treatment. Mesenchymal stromal cells (MSCs) are important candidates for tissue regeneration due to the release of bioactive factors, as well as antiapoptotic effects, scar inhibitors, and angiogenic effects. Studies have shown that MSCs act in various ways on injured tissue, such as immunomodulation of the inflamed environment, release of bioactive factors, restoration of axon myelin, prevention of neuronal apoptosis, and neuroregeneration. Current research using MSCs aims to prevent secondary injury, promote regeneration, and replace destroyed spinal cord tissue. This review presents information about the damage from primary and secondary events after SCI, treatments usually used, and preclinical and clinical results aiming at the cell therapy using MSCs as a tissue regeneration strategy.
{"title":"Mesenchymal stromal cells as a choice for spinal cord injury treatment","authors":"L. Fracaro, B. Zoehler, C. Rebelatto","doi":"10.20517/2347-8659.2019.009","DOIUrl":"https://doi.org/10.20517/2347-8659.2019.009","url":null,"abstract":"Spinal cord injury (SCI) is a serious clinical problem that affects approximately 17,500 new patients per year in the United States. The main causes of SCI are vehicle collisions, falls, violence (mainly gunshot wounds), and sports/recreational activities. The final severity of the damage results from primary and secondary mechanisms that begin at the time of injury and last for months after trauma. To reduce the extent of damage, several treatments have been proposed. This review summarizes results from several studies that have pointed to cell therapy as the main form of neuroregenerative treatment. Mesenchymal stromal cells (MSCs) are important candidates for tissue regeneration due to the release of bioactive factors, as well as antiapoptotic effects, scar inhibitors, and angiogenic effects. Studies have shown that MSCs act in various ways on injured tissue, such as immunomodulation of the inflamed environment, release of bioactive factors, restoration of axon myelin, prevention of neuronal apoptosis, and neuroregeneration. Current research using MSCs aims to prevent secondary injury, promote regeneration, and replace destroyed spinal cord tissue. This review presents information about the damage from primary and secondary events after SCI, treatments usually used, and preclinical and clinical results aiming at the cell therapy using MSCs as a tissue regeneration strategy.","PeriodicalId":19129,"journal":{"name":"Neuroimmunology and Neuroinflammation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48513453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-03-21DOI: 10.20517/2347-8659.2019.11
T. Astorino, Eric T. Harness
Aim: The decline in ambulation characteristic of spinal cord injury (SCI) dramatically modifies quality of life and body composition. To examine changes in quality of life, body satisfaction, and body composition in response to 6 months of activity-based therapy in individuals with spinal cord injury (SCI). Methods: Men and women with complete or incomplete SCI (12 with tetraplegia and 13 with paraplegia; mean age and duration of injury of 35.8 ± 12.9 years and 3.8 ± 5.5 years, respectively) completed 6 months of activity-based therapy consisting of load bearing, locomotor training, whole-body resistance training, functional electrical stimulation, and assisted/unassisted walking for 8.5 ± 4.3 h/week. At baseline and at 3 and 6 months of training, body satisfaction, perceived quality of life, depression, and bodily pain were assessed using various questionnaires, and whole-body and regional fat mass and fat-free mass were determined with dual-energy X-ray absorptiometry. One-way analysis of variance with repeated measures was used to examine changes in outcome measures during the study. Results: Measures of body satisfaction (+23%) and quality of life (+8%) were improved (P < 0.05) in response to training, yet no change in depression or pain was demonstrated (P > 0.05). Percent body fat increased (P = 0.02), yet no change (P > 0.05) was seen in whole-body or regional fat free mass. Conclusion: Data suggest that chronic high-volume activity-based therapy enhances various indices of quality of life in men and women with SCI, but may be an ineffective approach to reduce fat deposition and increase muscle mass after SCI. Original Article Astorino et al. Neuroimmunol Neuroinflammation 2020;7:40-50 I http://dx.doi.org/10.20517/2347-8659.2019.11 Page 41
{"title":"Improved quality of life and body satisfaction in response to activity-based therapy in adults with spinal cord injury","authors":"T. Astorino, Eric T. Harness","doi":"10.20517/2347-8659.2019.11","DOIUrl":"https://doi.org/10.20517/2347-8659.2019.11","url":null,"abstract":"Aim: The decline in ambulation characteristic of spinal cord injury (SCI) dramatically modifies quality of life and body composition. To examine changes in quality of life, body satisfaction, and body composition in response to 6 months of activity-based therapy in individuals with spinal cord injury (SCI). Methods: Men and women with complete or incomplete SCI (12 with tetraplegia and 13 with paraplegia; mean age and duration of injury of 35.8 ± 12.9 years and 3.8 ± 5.5 years, respectively) completed 6 months of activity-based therapy consisting of load bearing, locomotor training, whole-body resistance training, functional electrical stimulation, and assisted/unassisted walking for 8.5 ± 4.3 h/week. At baseline and at 3 and 6 months of training, body satisfaction, perceived quality of life, depression, and bodily pain were assessed using various questionnaires, and whole-body and regional fat mass and fat-free mass were determined with dual-energy X-ray absorptiometry. One-way analysis of variance with repeated measures was used to examine changes in outcome measures during the study. Results: Measures of body satisfaction (+23%) and quality of life (+8%) were improved (P < 0.05) in response to training, yet no change in depression or pain was demonstrated (P > 0.05). Percent body fat increased (P = 0.02), yet no change (P > 0.05) was seen in whole-body or regional fat free mass. Conclusion: Data suggest that chronic high-volume activity-based therapy enhances various indices of quality of life in men and women with SCI, but may be an ineffective approach to reduce fat deposition and increase muscle mass after SCI. Original Article Astorino et al. Neuroimmunol Neuroinflammation 2020;7:40-50 I http://dx.doi.org/10.20517/2347-8659.2019.11 Page 41","PeriodicalId":19129,"journal":{"name":"Neuroimmunology and Neuroinflammation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48451942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-02-21DOI: 10.20517/2347-8659.2019.16
Xiaodan Shi, Yi W. Li, Ying He, Rui Wu, Fang Du, Gang Zhao
Paraneoplastic cerebellar degeneration (PCD) can occur in patients with underlying cancer, such as small cell lung cancer (SCLC). Anti-CV2/CRMP5 antibodies are well-established biomarkers of PCD associated with SCLC, but cannot be detected in most situations. Recently, next-generation sequencing has been a promising technology to discover cancerdriven mutations, which provide an alternative strategy to accomplish ultra-early diagnosis of those patients. Here, we report the case of a 75-year-old man diagnosed with SCLC, who primarily presented with anti-CV2/CRMP5 antibodies positive PCD. Eight high-frequency gene mutations (TSC2 , DNMT1 , CIC , FGF6 , NSD1 , TSHR , CRLF2 , and EPPK1 ) were detected 7 months before diagnosis with no abnormalities of imaging or cerebrospinal fluid examination found initially. Therefore, this case suggests the possibility of detecting certain somatic mutations for the ultra-early diagnosis of patients presenting with PCD associated with SCLC.
{"title":"Paraneoplastic cerebellar degeneration associated with somatic mutations in ultra-early diagnosis of small cell lung cancer: a case report","authors":"Xiaodan Shi, Yi W. Li, Ying He, Rui Wu, Fang Du, Gang Zhao","doi":"10.20517/2347-8659.2019.16","DOIUrl":"https://doi.org/10.20517/2347-8659.2019.16","url":null,"abstract":"Paraneoplastic cerebellar degeneration (PCD) can occur in patients with underlying cancer, such as small cell lung cancer (SCLC). Anti-CV2/CRMP5 antibodies are well-established biomarkers of PCD associated with SCLC, but cannot be detected in most situations. Recently, next-generation sequencing has been a promising technology to discover cancerdriven mutations, which provide an alternative strategy to accomplish ultra-early diagnosis of those patients. Here, we report the case of a 75-year-old man diagnosed with SCLC, who primarily presented with anti-CV2/CRMP5 antibodies positive PCD. Eight high-frequency gene mutations (TSC2 , DNMT1 , CIC , FGF6 , NSD1 , TSHR , CRLF2 , and EPPK1 ) were detected 7 months before diagnosis with no abnormalities of imaging or cerebrospinal fluid examination found initially. Therefore, this case suggests the possibility of detecting certain somatic mutations for the ultra-early diagnosis of patients presenting with PCD associated with SCLC.","PeriodicalId":19129,"journal":{"name":"Neuroimmunology and Neuroinflammation","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42435407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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