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Cells May 2024This systematic review aims to gather evidence on the mechanisms triggered by diverse preconditioning strategies for mesenchymal stem cells (MSCs) and their impact on... (Review)
Review
This systematic review aims to gather evidence on the mechanisms triggered by diverse preconditioning strategies for mesenchymal stem cells (MSCs) and their impact on their potential to treat ischemic and traumatic injuries affecting the nervous system. The 52 studies included in this review report nine different types of preconditioning, namely, manipulation of oxygen pressure, exposure to chemical substances, lesion mediators or inflammatory factors, usage of ultrasound, magnetic fields or biomechanical forces, and culture in scaffolds or 3D cultures. All these preconditioning strategies were reported to interfere with cellular pathways that influence MSCs' survival and migration, alter MSCs' phenotype, and modulate the secretome and proteome of these cells, among others. The effects on MSCs' phenotype and characteristics influenced MSCs' performance in models of injury, namely by increasing the homing and integration of the cells in the lesioned area and inducing the secretion of growth factors and cytokines. The administration of preconditioned MSCs promoted tissue regeneration, reduced neuroinflammation, and increased angiogenesis and myelinization in rodent models of stroke, traumatic brain injury, and spinal cord injury. These effects were also translated into improved cognitive and motor functions, suggesting an increased therapeutic potential of MSCs after preconditioning. Importantly, none of the studies reported adverse effects or less therapeutic potential with these strategies. Overall, we can conclude that all the preconditioning strategies included in this review can stimulate pathways that relate to the therapeutic effects of MSCs. Thus, it would be interesting to explore whether combining different preconditioning strategies can further boost the reparative effects of MSCs, solving some limitations of MSCs' therapy, namely donor-associated variability.
Topics: Humans; Mesenchymal Stem Cells; Animals; Mesenchymal Stem Cell Transplantation; Nervous System Diseases
PubMed: 38786067
DOI: 10.3390/cells13100845 -
Revista Brasileira de Psiquiatria (Sao... 2024Evidence from diffusion tensor imaging (DTI) and postmortem studies has demonstrated white-matter (WM) deficits in bipolar disorder (BD). Changes in peripheral blood...
OBJECTIVES
Evidence from diffusion tensor imaging (DTI) and postmortem studies has demonstrated white-matter (WM) deficits in bipolar disorder (BD). Changes in peripheral blood biomarkers have also been observed; however, studies evaluating the potential relationship between brain alterations and the periphery are scarce. The objective of this systematic review is to investigate the relationship between blood-based biomarkers and WM in BD.
METHODS
PubMed, Embase, and PsycINFO were used to conduct literature searches. Cross-sectional or longitudinal studies reporting original data which investigated both a blood-based biomarker and WM (by neuroimaging) in BD were included.
RESULTS
Of 3,750 studies retrieved, 23 were included. Several classes of biomarkers were found to have a significant relationship with WM in BD. These included cytokines and growth factors (interleukin-8 [IL-8], tumor necrosis factor alpha [TNF-a], and insulin-like growth factor binding protein 3 [IGFBP-3]), innate immune system (natural killer cells [NK]), metabolic markers (lipid hydroperoxidase, cholesterol, triglycerides), the kynurenine (Kyn) pathway (5-hydroxyindoleacetic acid, kynurenic acid [Kyna]), and various gene polymorphisms (serotonin-transporter-linked promoter region).
CONCLUSION
This systematic review revealed that blood-based biomarkers are associated with markers of WM deficits observed in BD. Longitudinal studies investigating the potential clinical utility of these specific biomarkers are encouraged.
Topics: Bipolar Disorder; Humans; Biomarkers; White Matter; Myelin Sheath; Cytokines
PubMed: 38712923
DOI: 10.47626/1516-4446-2023-3267 -
NeuroImage. Clinical 2024Quantitative susceptibility mapping (QSM) is a quantitative measure based on magnetic resonance imaging sensitive to iron and myelin content. This makes QSM a promising... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Quantitative susceptibility mapping (QSM) is a quantitative measure based on magnetic resonance imaging sensitive to iron and myelin content. This makes QSM a promising non-invasive tool for multiple sclerosis (MS) in research and clinical practice.
OBJECTIVE
We performed a systematic review and meta-analysis on the use of QSM in MS.
METHODS
Our review was prospectively registered on PROSPERO (CRD42022309563). We searched five databases for studies published between inception and 30th April 2023. We identified 83 English peer-reviewed studies that applied QSM images on MS cohorts. Fifty-five included studies had at least one of the following outcome measures: deep grey matter QSM values in MS, either compared to healthy controls (HC) (k = 13) or correlated with the score on the Expanded Disability Status Scale (EDSS) (k = 7), QSM lesion characteristics (k = 22) and their clinical correlates (k = 17), longitudinal correlates (k = 11), histological correlates (k = 7), or correlates with other imaging techniques (k = 12). Two meta-analyses on deep grey matter (DGM) susceptibility data were performed, while the remaining findings could only be analyzed descriptively.
RESULTS
After outlier removal, meta-analyses demonstrated a significant increase in the basal ganglia susceptibility (QSM values) in MS compared to HC, caudate (k = 9, standardized mean difference (SDM) = 0.54, 95 % CI = 0.39-0.70, I = 46 %), putamen (k = 9, SDM = 0.38, 95 % CI = 0.19-0.57, I = 59 %), and globus pallidus (k = 9, SDM = 0.48, 95 % CI = 0.28-0.67, I = 60 %), whereas thalamic QSM values exhibited a significant reduction (k = 12, SDM = -0.39, 95 % CI = -0.66--0.12, I = 84 %); these susceptibility differences in MS were independent of age. Further, putamen QSM values positively correlated with EDSS (k = 4, r = 0.36, 95 % CI = 0.16-0.53, I = 0 %). Regarding rim lesions, four out of seven studies, representing 73 % of all patients, reported rim lesions to be associated with more severe disability. Moreover, lesion development from initial detection to the inactive stage is paralleled by increasing, plateauing (after about two years), and gradually decreasing QSM values, respectively. Only one longitudinal study provided clinical outcome measures and found no association. Histological data suggest iron content to be the primary source of QSM values in DGM and at the edges of rim lesions; further, when also considering data from myelin water imaging, the decrease of myelin is likely to drive the increase of QSM values within WM lesions.
CONCLUSIONS
We could provide meta-analytic evidence for DGM susceptibility changes in MS compared to HC; basal ganglia susceptibility is increased and, in the putamen, associated with disability, while thalamic susceptibility is decreased. Beyond these findings, further investigations are necessary to establish the role of QSM in MS for research or even clinical routine.
Topics: Humans; Multiple Sclerosis; Magnetic Resonance Imaging; Gray Matter; Brain
PubMed: 38582068
DOI: 10.1016/j.nicl.2024.103598 -
PloS One 2024Multiple Sclerosis (MS) is an autoimmune disease affecting the central nervous system, characterised by neuroinflammation and neurodegeneration. Fatigue and depression...
Multiple Sclerosis (MS) is an autoimmune disease affecting the central nervous system, characterised by neuroinflammation and neurodegeneration. Fatigue and depression are common, debilitating, and intertwined symptoms in people with relapsing-remitting MS (pwRRMS). An increased understanding of brain changes and mechanisms underlying fatigue and depression in RRMS could lead to more effective interventions and enhancement of quality of life. To elucidate the relationship between depression and fatigue and brain connectivity in pwRRMS we conducted a systematic review. Searched databases were PubMed, Web-of-Science and Scopus. Inclusion criteria were: studied participants with RRMS (n ≥ 20; ≥ 18 years old) and differentiated between MS subtypes; published between 2001-01-01 and 2023-01-18; used fatigue and depression assessments validated for MS; included brain structural, functional magnetic resonance imaging (fMRI) or diffusion MRI (dMRI). Sixty studies met the criteria: 18 dMRI (15 fatigue, 5 depression) and 22 fMRI (20 fatigue, 5 depression) studies. The literature was heterogeneous; half of studies reported no correlation between brain connectivity measures and fatigue or depression. Positive findings showed that abnormal cortico-limbic structural and functional connectivity was associated with depression. Fatigue was linked to connectivity measures in cortico-thalamic-basal-ganglial networks. Additionally, both depression and fatigue were related to altered cingulum structural connectivity, and functional connectivity involving thalamus, cerebellum, frontal lobe, ventral tegmental area, striatum, default mode and attention networks, and supramarginal, precentral, and postcentral gyri. Qualitative analysis suggests structural and functional connectivity changes, possibly due to axonal and/or myelin loss, in the cortico-thalamic-basal-ganglial and cortico-limbic network may underlie fatigue and depression in pwRRMS, respectively, but the overall results were inconclusive, possibly explained by heterogeneity and limited number of studies. This highlights the need for further studies including advanced MRI to detect more subtle brain changes in association with depression and fatigue. Future studies using optimised imaging protocols and validated depression and fatigue measures are required to clarify the substrates underlying these symptoms in pwRRMS.
Topics: Humans; Brain; Depression; Fatigue; Magnetic Resonance Imaging; Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Quality of Life; Adult
PubMed: 38551913
DOI: 10.1371/journal.pone.0299634 -
Journal of Psychiatric Research May 2024Iron deficiency may play a role in the pathophysiology of Attention Deficit/Hyperactivity Disorder (ADHD). Due to its preponderant function in monoamine catecholamine... (Review)
Review
Iron deficiency may play a role in the pathophysiology of Attention Deficit/Hyperactivity Disorder (ADHD). Due to its preponderant function in monoamine catecholamine and myelin synthesis, brain iron concentration may be of primary interest in the investigation of iron dysregulation in ADHD. This study reviewed current evidence of brain iron abnormalities in children and adolescents with ADHD using magnetic resonance imaging methods, such as relaxometry and quantitative susceptibility mapping, to assess brain iron estimates. The study was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A literature search was performed for studies published between January 1, 2008 and July 7, 2023 in Medline, Scopus and Proquest. Regions of interest, brain iron index values and phenotypical information were extracted from the relevant studies. Risk of bias was assessed using a modified version of the National Heart, Lung, and Blood Institute quality assessment tool. Seven cross-sectional studies comparing brain iron estimates in children with ADHD with neurotypical children were included. Significantly reduced brain iron content in medication-naïve children with ADHD was a consistent finding. Two studies found psychostimulant use may increase and normalize brain iron concentration in children with ADHD. The findings were consistent across the studies despite differing methodologies and may lay the early foundation for the recognition of a potential biomarker in ADHD, although longitudinal prospective neuroimaging studies using larger sample sizes are required. Lastly, the effects of iron supplementation on brain iron concentration in children with ADHD need to be elucidated.
Topics: Child; Adolescent; Humans; Attention Deficit Disorder with Hyperactivity; Cross-Sectional Studies; Iron; Prospective Studies; Brain; Neuroimaging
PubMed: 38547742
DOI: 10.1016/j.jpsychires.2024.03.035 -
Brain Connectivity May 2024The subventricular zone promotes remyelination through activation differentiation of oligodendroglial precursor cells (OPCs) and neural stem cells (NSCs) into mature...
The subventricular zone promotes remyelination through activation differentiation of oligodendroglial precursor cells (OPCs) and neural stem cells (NSCs) into mature oligodendrocytes and thus in the adult brain. In multiple sclerosis (MS) this regenerative capability is halted resulting in neurodegeneration. We aimed to systematically search and synthesize evidence on mechanisms and phenomena associated with subventricular zone (SVZ) dysfunction in MS. Our systematic review was reported according to the PRISMA-ScR statement. MEDLINE, SCOPUS, ProQuest, and Google Scholar were searched using the terms "subventricular zone" and "multiple sclerosis," including English-written and postmortem studies. Twenty studies were included. Thirteen studies on models of experimental autoimmune encephalomyelitis (EAE) reported among others strong stathmin immunoreactivity in the SVZ of EAE models, the role of MOG immunization in neurogenesis impairment, the effect of parenchymal OPCs and NSCs in myelin repair, and the importance of ependymal cells (E1/E2) and ciliated B1 cells in SVZ stem cell signaling. CXCR4 signaling and transcriptional profiles of SVZ microglia, Gli1 pathway, and galactin-3 were also explored. Studies in humans demonstrated microstructural SVZ damage in progressive MS and the persistence of black holes near the SVZ, whereas postmortem confirmed the generation of polysialic acid-neural cell adhesion molecule and NG2-positive progenitors through SVZ activation, SVZ stathmin immunoreactivity, Shh pathway, and Gal-3 upregulation. Oligodendrogenesis defects translate to reduced remyelination, a hallmark of MS that determines its end-phenotype and disease course. The role of inflammation and subsequent SVZ microenvironment disruption is evident in MS pathology.
Topics: Animals; Humans; Cell Differentiation; Encephalomyelitis, Autoimmune, Experimental; Lateral Ventricles; Multiple Sclerosis; Neural Stem Cells; Neurogenesis; Oligodendroglia
PubMed: 38534961
DOI: 10.1089/brain.2023.0081 -
World Neurosurgery Jun 2024Schwannomas are benign peripheral nerve sheath tumors arising from myelinating Schwann cells. Although macrocystic changes are regularly encountered in schwannoma... (Review)
Review
BACKGROUND
Schwannomas are benign peripheral nerve sheath tumors arising from myelinating Schwann cells. Although macrocystic changes are regularly encountered in schwannoma variants such as vestibular nerve tumors, they are exceedingly rare among spinal neoplasms.
METHODS
Case report and systematic review of 4 databases (Ovid Medline, PubMed, Science Direct, and SCOPUS) from inception to present. All peer-reviewed publications reporting intradural cystic thoracic schwannoma were included.
RESULTS
We identified 8 publications documenting 9 cases of cystic thoracic schwannoma. Four were female, 5 male; median age was 41 years (range, 27-80). Presentations ranged from incidental to pain, sensory changes, lower extremity paresis, or bowel/bladder dysfunction. Characteristic radiographic findings included T1 hypointensity, T2 hyperintensity, and cord effacement or compression. The present case followed a similar pattern: a 52-year-old male presented with worsening bilateral lower extremity weakness, low back pain, and gait dysfunction, worsening over 3 days. Examination also revealed decreased left lower extremity sensation. Imaging identified a well-delineated intradural, extramedullary macrocystic extending over T7-T10. The patient underwent a laminectomy resulting in complete tumor resection and restoration of intact neurologic function. Final pathology confirmed benign cystic schwannoma.
CONCLUSIONS
Macrocystic thoracic schwannomas are exceedingly rare and lack a comprehensive scheme for clinical classification of their natural history and pathogenesis. We report the 10th case of such a schwannoma, and the first associated systematic review. Although macrocystic thoracic schwannomas are not frequently encountered, accurate diagnosis and appropriate neurosurgical treatment is critical in these vulnerable patients, given the opportunity for excellent functional outcomes following neurosurgical treatment.
Topics: Humans; Neurilemmoma; Male; Middle Aged; Thoracic Vertebrae; Female; Spinal Cord Neoplasms; Adult; Aged
PubMed: 38522790
DOI: 10.1016/j.wneu.2024.03.091 -
International Journal of Molecular... Feb 2024A spinal cord injury (SCI) causes changes in brain structure and brain function due to the direct effects of nerve damage, secondary mechanisms, and long-term effects of... (Review)
Review
A spinal cord injury (SCI) causes changes in brain structure and brain function due to the direct effects of nerve damage, secondary mechanisms, and long-term effects of the injury, such as paralysis and neuropathic pain (NP). Recovery takes place over weeks to months, which is a time frame well beyond the duration of spinal shock and is the phase in which the spinal cord remains unstimulated below the level of injury and is associated with adaptations occurring throughout the nervous system, often referred to as neuronal plasticity. Such changes occur at different anatomical sites and also at different physiological and molecular biological levels. This review aims to investigate brain plasticity in patients with SCIs and its influence on the rehabilitation process. Studies were identified from an online search of the PubMed, Web of Science, and Scopus databases. Studies published between 2013 and 2023 were selected. This review has been registered on OSF under (n) 9QP45. We found that neuroplasticity can affect the sensory-motor network, and different protocols or rehabilitation interventions can activate this process in different ways. Exercise rehabilitation training in humans with SCIs can elicit white matter plasticity in the form of increased myelin water content. This review has demonstrated that SCI patients may experience plastic changes either spontaneously or as a result of specific neurorehabilitation training, which may lead to positive outcomes in functional recovery. Clinical and experimental evidence convincingly displays that plasticity occurs in the adult CNS through a variety of events following traumatic or non-traumatic SCI. Furthermore, efficacy-based, pharmacological, and genetic approaches, alone or in combination, are increasingly effective in promoting plasticity.
Topics: Humans; Spinal Cord Injuries; Spinal Cord; Brain; Neuronal Plasticity; Recovery of Function
PubMed: 38396902
DOI: 10.3390/ijms25042224 -
Frontiers in Immunology 2024The purpose of this study was to investigate the current research status, focus areas, and developmental trends in the field of Myelin oligodendrocyte glycoprotein...
OBJECTIVE
The purpose of this study was to investigate the current research status, focus areas, and developmental trends in the field of Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) through an analysis of scientific literature.
METHODS
The relevant research articles on MOGAD published from 1947 to 2022 were retrieved from the Web of Science database. The quantitative output of MOGAD related research articles, their distribution by country/region, data on collaborative publishing, influential authors, high-yield institutions, keywords, hotspots, and development trends were analyzed. Additionally, visual knowledge maps were generated using VOSviewer and Citespace.
RESULTS
There has been a steady increase in the number of MOGAD related publications indicating that the subject has garnered increasing interest among researchers globally. The United States has been the leading contributor with 496 papers (19.25%), followed by China (244, 9.63%), Japan (183, 7.10%), the United Kingdom (154, 5.98%), and Germany (149, 5.78%). Among these countries, the United Kingdom boasts the highest citation frequency at the rate of 46.49 times per paper. Furthermore, active collaboration in MOGAD related research is observed primarily between the United States and countries such as Canada, Germany, Australia, Italy, the United Kingdom and Japan. Mayo Clinic ranks first in total articles published (109) and frequency of citations per article (77.79). Takahashi Toshiyuki from Tohoku University is the most prolific author, while is the most widely read journal in this field. "Disease Phenotype", "Treatment", "Novel Coronavirus Infection and Vaccination", "Immunopathological Mechanisms", "Clinical characteristics of children" and "Prognosis" are the primary keywords clusters in this field. "Novel Coronavirus Infection and Vaccination" and "Immunopathological Mechanisms" are research hotspots and have great development potential.
CONCLUSION
The past three decades have witnessed a significant expansion of research on MOGAD. The pathogenetic mechanism of MOGAD is poised to be the prominent research focus in this field in the foreseeable future.
Topics: Humans; Bibliometrics; Neuroinflammatory Diseases
PubMed: 38370410
DOI: 10.3389/fimmu.2024.1278867 -
Journal of Alzheimer's Disease : JAD 2024The clinical features of posterior cortical atrophy (PCA), a rare condition often caused by Alzheimer's disease, have been recently defined, while little is known about...
BACKGROUND
The clinical features of posterior cortical atrophy (PCA), a rare condition often caused by Alzheimer's disease, have been recently defined, while little is known about its neurophysiological correlates.
OBJECTIVE
To describe neurophysiological alterations of the visual pathway as assessed using visual field test (VF), visual evoked potentials (VEP), and electroretinogram (ERG) in PCA patients.
METHODS
Studies reporting VF, VEPs, and ERG in PCA patients were selected according PRISMA method. Of the 323 articles that emerged from the literature, 17 included the outcomes of interest. To these data, we added those derived from a patient cohort enrolled at our clinic.
RESULTS
The literature review included 140 patients, half of them (50%) presented with homonymous hemianopia or quadrantanopia. VEPs were available in 4 patients (2 normal findings, 1 decreased amplitude, and 1 increased latency) and ERG in 3 patients (substantially normal findings). Our case series included 6 patients, presenting with homonymous lateral hemianopia in 50% and contralateral cortical atrophy. VEPs showed normal amplitude in 66-83% according to the stimulation check, and increased latency in 67% in absence of myelin damage on MRI. Latency was increased in both eyes in 50% and only on one side in the other 50%. Such alterations were observed in patients with more severe and symmetric atrophy. ERG showed normal findings.
CONCLUSIONS
Neurophysiological investigations of the visual pathway in PCA are almost absent in literature. Alterations involve both amplitude and latency and can be also monocular. A multiple-point involvement of the optical pathway can be hypothesized.
Topics: Humans; Visual Pathways; Evoked Potentials, Visual; Neurodegenerative Diseases; Electroretinography; Atrophy
PubMed: 38363610
DOI: 10.3233/JAD-231123