Multiple system atrophy (MSA) is a severe α-synucleinopathy facilitated by glial reactions; the cerebellar variant (MSA-C) preferentially involves olivopontocerebellar fibres with conspicuous demyelination. A lack of aggressive models that preferentially involve olivopontocerebellar tracts in adulthood has hindered our understanding of the mechanisms of demyelination and neuroaxonal loss, and thus the development of effective treatments for MSA. We therefore aimed to develop a rapidly progressive mouse model that recaptures MSA-C pathology.
View Article and Find Full Text PDFBackground: Recent developments in the retinal hyperspectral imaging method have indicated its potential in addressing challenges posed by neurodegenerative disorders, such as Alzheimer's disease. This human clinical study is the first to assess reflectance spectra obtained from this imaging as a tool for diagnosing patients with Parkinson's disease (PD).
Methods: Retinal hyperspectral imaging was conducted on a total of 40 participants, including 20 patients with PD and 20 controls.
Background: Functionally impaired variants of , encoding an enzyme in biosynthesis of coenzyme Q10 (CoQ10), were found in familial multiple system atrophy (MSA) and V393A in is associated with sporadic MSA. Furthermore, reduced levels of CoQ10 have been demonstrated in MSA patients.
Methods: This study was a multicentre, randomised, double-blinded, placebo-controlled phase 2 trial.
Connexin 30 (Cx30), which forms gap junctions between astrocytes, regulates cell adhesion and migration, and modulates glutamate transport. Cx30 is upregulated on activated astroglia in central nervous system inflammatory lesions, including spinal cord lesions in mutant superoxide dismutase 1 (mSOD1) transgenic amyotrophic lateral sclerosis (ALS) model mice. Here, we investigated the role of Cx30 in mSOD1 mice.
View Article and Find Full Text PDFA 44-year-old male was admitted to our hospital because of sudden weakness and sensory loss in both legs following left scapular pain. He had a history of lower back pain but no vascular risk factors. Neurological examination on admission revealed flaccid paraplegia, a loss of both pinprick and vibratory sensations below the Th6 level, and bladder and rectal disturbances.
View Article and Find Full Text PDFWe report a 60-year-old male with anti-myelin oligodendrocyte glycoprotein (MOG) antibody who developed progressive cognitive deterioration and behavioral changes, with no other focal signs, over 9 months. MRI showed numerous T2-hyperintense lesions with partial contrast enhancement in white and grey matter of cerebrum, cerebellum and spinal cord. A brain biopsy revealed perivascular inflammatory cell infiltration, disturbed vascular continuity and no demyelination, indicative of a lymphocytic pattern of primary CNS vasculitis (PCNSV).
View Article and Find Full Text PDFBackground: Hopkins syndrome (HS) is a rare disorder presenting with acute flaccid paralysis of the limbs following an asthma attack. Neurologists encounter a diagnostic challenge if patients without a history of bronchial asthma develop neurologic features mimicking HS following acute respiratory distress. We report a case of HS occurring after a first episode of bronchial asthma associated with enterovirus D68 infection.
View Article and Find Full Text PDFAnn Clin Transl Neurol
October 2015
Background: Fingolimod efficiently reduces multiple sclerosis (MS) relapse by inhibiting lymphocyte egress from lymph nodes through down-modulation of sphingosine 1-phosphate (S1P) receptors. We aimed to clarify the alterations in peripheral blood T cell subsets associated with MS relapse on fingolimod.
Methods/principal Findings: Blood samples successively collected from 23 relapsing-remitting MS patients before and during fingolimod therapy (0.
Cells Tissues Organs
November 2015
Schwann cells form myelin, sustain axons and provide the microenvironment for nerve fibers, thereby playing a key role in the peripheral nervous system (PNS). Schwann cells also provide support for the damaged PNS by producing factors that strongly promote axonal regrowth and contribute to remyelination, which is crucial for the recovery of neural function. These advantages are not confined to the PNS and also apply to the central nervous system.
View Article and Find Full Text PDFJ Neurol Neurosurg Psychiatry
January 2016
Objectives: To clarify the clinical features of combined central and peripheral demyelination (CCPD) via a nationwide survey.
Methods: The following characteristics were used to define CCPD: T2 high-signal intensity lesions in the brain, optic nerves or spinal cord on MRI, or abnormalities on visual-evoked potentials; conduction delay, conduction block, temporal dispersion or F-wave abnormalities suggesting demyelinating neuropathy based on nerve conduction studies; exclusion of secondary demyelination. We conducted a nationwide survey in 2012, sending questionnaires to 1332 adult and paediatric neurology institutions in Japan.
Data regarding vitamin D in multiple sclerosis (MS) in Asia are limited. We investigated whether Japanese MS patients show decreased serum 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)2D], and vitamin D-binding protein (DBP) during winter. Mean serum 25(OH)D and 1,25(OH)2D levels were significantly lower in MS patients than in controls.
View Article and Find Full Text PDFObjective: We report the clinical application of intravoxel incoherent motion (IVIM) magnetic resonance (MR) imaging to diagnose a case of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) in the acute phase.
Results: On IVIM MR Images of this patient, higher perfusion (f) and diffusion (D) values in the left occipital and temporal lobes were found compared to the contralateral areas.
Conclusion: These findings imply a breakdown of autoregulation with hyperperfusion and vasogenic edema during the acute phase of MELAS, as described in previous reports.
Objectives: We aimed to identify the target antigens for combined central and peripheral demyelination (CCPD).
Methods: We screened target antigens by immunohistochemistry and immunoblotting using peripheral nerve tissues to identify target antigens recognized by serum antibodies from selected CCPD and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) cases. We then measured the level of antibody to the relevant antigen in 7 patients with CCPD, 16 patients with CIDP, 20 patients with multiple sclerosis, 20 patients with Guillain-Barré syndrome, 21 patients with other neuropathies, and 23 healthy controls (HC) by ELISA and cell-based assays using HEK293 cells.
Unlabelled: Besides stimulating angiogenesis or cell survival, basic fibroblast growth factor (bFGF) has the potential for protecting neurons in the injured spinal cord.
Objective: To investigate the effects of a sustained-release system of bFGF from gelatin hydrogel (GH) in a rat spinal cord contusion model.
Methods: Adult female Sprague-Dawley rats were subjected to a spinal cord contusion injury at the T10 vertebral level using an IH impactor (200 kdyn).
Background: Differences in cytokine/chemokine profiles among patients with neuromyelitis optica (NMO), relapsing remitting multiple sclerosis (RRMS), and primary progressive MS (PPMS), and the relationships of these profiles with clinical and neuroimaging features are unclear. A greater understanding of these profiles may help in differential diagnosis.
Methods/principal Findings: We measured 27 cytokines/chemokines and growth factors in CSF collected from 20 patients with NMO, 26 with RRMS, nine with PPMS, and 18 with other non-inflammatory neurological diseases (OND) by multiplexed fluorescent bead-based immunoassay.
A cell-based therapy for the replacement of dopaminergic neurons has been a long-term goal in Parkinson's disease research. Here, we show that autologous engraftment of A9 dopaminergic neuron-like cells induced from mesenchymal stem cells (MSCs) leads to long-term survival of the cells and restoration of motor function in hemiparkinsonian macaques. Differentiated MSCs expressed markers of A9 dopaminergic neurons and released dopamine after depolarization in vitro.
View Article and Find Full Text PDFThe stochastic and elite models have been proposed for the mechanism of induced pluripotent stem (iPS) cell generation. In this study we report a system that supports the elite model. We previously identified multilineage-differentiating stress-enduring (Muse) cells in human dermal fibroblasts that are characterized by stress tolerance, expression of pluripotency markers, self-renewal, and the ability to differentiate into endodermal-, mesodermal-, and ectodermal-lineage cells from a single cell.
View Article and Find Full Text PDFBone marrow stromal cells (MSCs) are a useful source of cells because of their abundant supply and few associated ethical problems. We have previously reported that neural progenitor cells (NS-MSCs) can be effectively induced from MSCs and differentiate into neurons to contribute to functional recovery when transplanted into the rat stroke model. In this study, we attempted to enhance the therapeutic effects of NS-MSCs with a collagen sponge and basic fibroblast growth factor (bFGF) releasing microspheres.
View Article and Find Full Text PDFHuman umbilical cord-derived mesenchymal stromal cells (UC-MSCs) that are available from cell banks can be induced to differentiate into various cell types, thereby making them practical potential sources for cell-based therapies. In injured peripheral nerves, Schwann cells (SCs) contribute to functional recovery by supporting axonal regeneration and myelin reconstruction. Here, we first demonstrate a system to induce UC-MSCs to differentiate into cells with SC properties (UC-SCs) by treatment with β-mercaptoethanol followed by retinoic acid and a set of specific cytokines.
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