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Clinical and Translational Imaging 2020Diffusion tensor magnetic resonance imaging (DTI) characterises tissue microstructure and provides proxy measures of myelination, axon diameter, fibre density and... (Review)
Review
PURPOSE
Diffusion tensor magnetic resonance imaging (DTI) characterises tissue microstructure and provides proxy measures of myelination, axon diameter, fibre density and organisation. This may be valuable in the assessment of the roots of the brachial plexus in health and disease. Therefore, there is a need to define the normal DTI values.
METHODS
The literature was systematically searched for studies of asymptomatic adults who underwent DTI of the brachial plexus. Participant characteristics, scanning protocols, and measurements of the fractional anisotropy (FA) and mean diffusivity (MD) of each spinal root were extracted by two independent review authors. Generalised linear modelling was used to estimate the effect of experimental conditions on the FA and MD. Meta-analysis of root-level estimates was performed using Cohen's method with random effects.
RESULTS
Nine articles, describing 316 adults (1:1 male:female) of mean age 35 years (SD 6) were included. Increments of ten diffusion sensitising gradient directions reduced the mean FA by 0.01 (95% CI 0.01, 0.03). Each year of life reduced the mean MD by 0.03 × 10 mm/s (95% CI 0.01, 0.04). At 3-T, the pooled mean FA of the roots was 0.36 (95% CI 0.34, 0.38; 98%). The pooled mean MD of the roots was 1.51 × 10 mm/s (95% CI 1.45, 1.56; 99%).
CONCLUSIONS
The FA and MD of the roots of the brachial plexus vary according to experimental conditions and participant factors. We provide summary estimates of the normative values in different conditions which may be valuable to researchers and clinicians alike.
PubMed: 33282795
DOI: 10.1007/s40336-020-00393-x -
Multiple Sclerosis (Houndmills,... Jan 2022Immune-mediated demyelination and consequent degeneration of oligodendrocytes and axons are hallmark features of multiple sclerosis (MS). Remyelination declines in...
BACKGROUND
Immune-mediated demyelination and consequent degeneration of oligodendrocytes and axons are hallmark features of multiple sclerosis (MS). Remyelination declines in progressive MS, causing permanent axonal loss and irreversible disabilities. Strategies aimed at enhancing remyelination are critical to attenuate disease progression.
OBJECTIVE
We systematically reviewed recent advances in neuroprotective and regenerative therapies for MS, covering preclinical and clinical studies.
METHODS
We searched three biomedical databases using defined keywords. Two authors independently reviewed articles for inclusion based on pre-specified criteria. The data were extracted from each study and assessed for risk of bias.
RESULTS
Our search identified 7351 studies from 2014 to 2020, of which 221 met the defined criteria. These studies reported 262 interventions, wherein 92% were evaluated in animal models. These interventions comprised protein, RNA, lipid and cellular biologics, small molecules, inorganic compounds, and dietary and physiological interventions. Small molecules were the most highly represented strategy, followed by antibody therapies and stem cell transplantation.
CONCLUSION
While significant strides have been made to develop regenerative treatments for MS, the current evidence illustrates a skewed representation of the types of strategies that advance to clinical trials. Further examination is thus required to address current barriers to implementing experimental treatments in clinical settings.
Topics: Animals; Axons; Multiple Sclerosis; Myelin Sheath; Nerve Regeneration; Oligodendroglia; Remyelination
PubMed: 33870797
DOI: 10.1177/13524585211008760 -
Cells Jan 2022Cell-based therapy is a promising treatment to favor tissue healing through less invasive strategies. Mesenchymal stem cells (MSCs) highlighted as potential candidates...
Cell-based therapy is a promising treatment to favor tissue healing through less invasive strategies. Mesenchymal stem cells (MSCs) highlighted as potential candidates due to their angiogenic, anti-apoptotic and immunomodulatory properties, in addition to their ability to differentiate into several specialized cell lines. Cells can be carried through a biological delivery system, such as fibrin glue, which acts as a temporary matrix that favors cell-matrix interactions and allows local and paracrine functions of MSCs. Thus, the aim of this systematic review was to evaluate the potential of fibrin glue combined with MSCs in nerve regeneration. The bibliographic search was performed in the PubMed/MEDLINE, Web of Science and Embase databases, using the descriptors ("fibrin sealant" OR "fibrin glue") AND "stem cells" AND "nerve regeneration", considering articles published until 2021. To compose this review, 13 in vivo studies were selected, according to the eligibility criteria. MSCs favored axonal regeneration, remyelination of nerve fibers, as well as promoted an increase in the number of myelinated fibers, myelin sheath thickness, number of axons and expression of growth factors, with significant improvement in motor function recovery. This systematic review showed clear evidence that fibrin glue combined with MSCs has the potential to regenerate nervous system lesions.
Topics: Fibrin Tissue Adhesive; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Models, Biological; Nerve Regeneration; Nerve Tissue
PubMed: 35053336
DOI: 10.3390/cells11020221 -
Brain Sciences Jan 2023(1) Background: Multiple sclerosis (MS) is an immune system disease in which myelin in the nervous system is affected. This abnormal immune system mechanism causes... (Review)
Review
(1) Background: Multiple sclerosis (MS) is an immune system disease in which myelin in the nervous system is affected. This abnormal immune system mechanism causes physical disabilities and cognitive impairment. Functional magnetic resonance imaging (fMRI) is a common neuroimaging technique used in studying MS. Computational methods have recently been applied for disease detection, notably graph theory, which helps researchers understand the entire brain network and functional connectivity. (2) Methods: Relevant databases were searched to identify articles published since 2000 that applied graph theory to study functional brain connectivity in patients with MS based on fMRI. (3) Results: A total of 24 articles were included in the review. In recent years, the application of graph theory in the MS field received increased attention from computational scientists. The graph-theoretical approach was frequently combined with fMRI in studies of functional brain connectivity in MS. Lower EDSSs of MS stage were the criteria for most of the studies (4) Conclusions: This review provides insights into the role of graph theory as a computational method for studying functional brain connectivity in MS. Graph theory is useful in the detection and prediction of MS and can play a significant role in identifying cognitive impairment associated with MS.
PubMed: 36831789
DOI: 10.3390/brainsci13020246 -
Frontiers in Neurology 2020Structural brain white matter (WM) changes such as axonal caliber, density, myelination, and orientation, along with WM-dependent structural connectivity, may be...
Structural brain white matter (WM) changes such as axonal caliber, density, myelination, and orientation, along with WM-dependent structural connectivity, may be impacted early in Parkinson disease (PD). Diffusion magnetic resonance imaging (dMRI) has been used extensively to understand such pathological WM changes, and the focus of this systematic review is to understand both the methods utilized and their corresponding results in the context of early-stage PD. Diffusion tensor imaging (DTI) is the most commonly utilized method to probe WM pathological changes. Previous studies have suggested that DTI metrics are sensitive in capturing early disease-associated WM changes in preclinical symptomatic regions such as olfactory regions and the substantia nigra, which is considered to be a hallmark of PD pathology and progression. Postprocessing analytic approaches include region of interest-based analysis, voxel-based analysis, skeletonized approaches, and connectome analysis, each with unique advantages and challenges. While DTI has been used extensively to study WM disorganization in early-stage PD, it has several limitations, including an inability to resolve multiple fiber orientations within each voxel and sensitivity to partial volume effects. Given the subtle changes associated with early-stage PD, these limitations result in inaccuracies that severely impact the reliability of DTI-based metrics as potential biomarkers. To overcome these limitations, advanced dMRI acquisition and analysis methods have been employed, including diffusion kurtosis imaging and q-space diffeomorphic reconstruction. The combination of improved acquisition and analysis in DTI may yield novel and accurate information related to WM-associated changes in early-stage PD. In the current article, we present a systematic and critical review of dMRI studies in early-stage PD, with a focus on recent advances in DTI methodology. Yielding novel metrics, these advanced methods have been shown to detect diffuse WM changes in early-stage PD. These findings support the notion of early axonal damage in PD and suggest that WM pathology may go unrecognized until symptoms appear. Finally, the advantages and disadvantages of different dMRI techniques, analysis methods, and software employed are discussed in the context of PD-related pathology.
PubMed: 32477235
DOI: 10.3389/fneur.2020.00314 -
Frontiers in Pharmacology 2022The Na/K-ATPase is an integral membrane ion pump, essential to maintaining osmotic balance in cells in the presence of cardiotonic steroids; more specifically, ouabain...
The Na/K-ATPase is an integral membrane ion pump, essential to maintaining osmotic balance in cells in the presence of cardiotonic steroids; more specifically, ouabain can be an endogenous modulator of the Na/K-ATPase. Here, we conducted a systematic review of the effects of cardiotonic steroids on Ca in the brain of rats and mice. Methods: The review was carried out using the PubMed, Virtual Health Library, and EMBASE databases (between 12 June 2020 and 30 June 2020) and followed the guidelines described in the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). Results: in total, 829 references were identified in the electronic databases; however, only 20 articles were considered, on the basis of the inclusion criteria. The studies demonstrated the effects of ouabain on Ca signaling in synaptosomes, brain slices, and cultures of rat and mouse cells. In addition to the well-known cytotoxic effects of high doses of ouabain, resulting from indirect stimulation of the reverse mode of the Na/Ca exchanger and increased intracellular Ca, other effects have been reported. Ouabain-mediated Ca signaling was able to act increasing cholinergic, noradrenergic and glutamatergic neurotransmission. Furthermore, ouabain significantly increased intracellular signaling molecules such as InsPs, IP3 and cAMP. Moreover treatment with low doses of ouabain stimulated myelin basic protein synthesis. Ouabain-induced intracellular Ca increase may promote the activation of important cell signaling pathways involved in cellular homeostasis and function. Thus, the study of the application of ouabain in low doses being promising for application in neurological diseases. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020204498, identifier CRD42020204498.
PubMed: 36105192
DOI: 10.3389/fphar.2022.916312 -
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 -
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 -
Case Reports in Medicine 2020Lethal congenital contracture syndrome type 7 (LCCS7) and congenital hypomyelinating neuropathy type 3 (CHN3) are rare autosomal recessive diseases, characterized by...
Lethal congenital contracture syndrome type 7 (LCCS7) and congenital hypomyelinating neuropathy type 3 (CHN3) are rare autosomal recessive diseases, characterized by severe neonatal hypotonia, polyhydramnios, arthrogryposis, facial diplegia, and severe motor paralysis, leading to death in early infancy. They are related to mutations in the (contactin associated protein 1) gene, playing an important role in myelination. Recent studies have shown that both diseases could present with a wide phenotypic spectrum, with promising survival up to early childhood. We report on a 7-year-old boy from a nonconsanguineous Lebanese family presenting with neonatal hypotonia, respiratory distress, and arthrogryposis. Molecular analysis revealed the presence of a pathogenic variant in the gene leading to a premature stop codon: NM_003632.2:c.3361C>T p.(Arg1121 ). A review of the literature is discussed.
PubMed: 32328110
DOI: 10.1155/2020/8795607 -
Cureus Jun 2023Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune disorder that was first described in the late 1800s as a variant of multiple sclerosis (MS). However,...
Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune disorder that was first described in the late 1800s as a variant of multiple sclerosis (MS). However, it has recently been categorized, as a disease, especially with the discovery of aquaporin-4 (AQP4-Ab) and myelin oligodendrocyte glycoprotein antibodies (MOG-Ab). Unfortunately, patient presentation is not always clear, and NMOSD may initially be diagnosed as an alternative neurological disease. We present a 58-year-old woman who was hospitalized several times for what was initially perceived as a pontine stroke. However, given worsening symptoms, serologic testing confirmed AQP4-Ab positivity and, subsequently, the NMOSD diagnosis. In addition to the case report, a systematic literature review was performed to identify NMOSD cases initially misdiagnosed as stroke. Publications were selected and curated in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Six NMOSD patients were initially thought to have had acute strokes. However, steady progression and/or the recurrence of symptoms suggested that further investigations with neuroimaging studies and serological immune assays were necessary to exclude alternative etiologies. Notably, the age at onset in all cases was significantly more advanced than patients with typical NMOSD presentations (median age 32-41). In conclusion, the NMOSD diagnosis should be considered in cases with atypical stroke-like presentations, particularly those of later onset (defined as equal to or greater than 50 years of age). This is important as early recognition and treatment with immune therapies can improve functional outcomes.
PubMed: 37519518
DOI: 10.7759/cureus.41099