A5009538524- Multiple Sclerosis Research Studies
- Neurogenesis and neuroplasticity mechanisms
- Atherosclerosis and Cardiovascular Diseases
- Neuroinflammation and Neurodegeneration Mechanisms
- Peripheral Neuropathies and Disorders
- Complement system in diseases
- Cell Image Analysis Techniques
- Advanced Neuroimaging Techniques and Applications
- Prion Diseases and Protein Misfolding
- Cytokine Signaling Pathways and Interactions
- Systemic Lupus Erythematosus Research
- Advanced MRI Techniques and Applications
- Immunotherapy and Immune Responses
- RNA regulation and disease
- Immune Response and Inflammation
- MicroRNA in disease regulation
- Cellular Mechanics and Interactions
- T-cell and B-cell Immunology
- Inflammasome and immune disorders
- Immune cells in cancer
- Radiomics and Machine Learning in Medical Imaging
- Elasticity and Material Modeling
- Coronary Interventions and Diagnostics
- Blood properties and coagulation
- Cancer, Lipids, and Metabolism
Queen Mary University of London
2014-2024
Imperial College London
2010-2021
Lung Institute
2010-2021
Hammersmith Hospital
2011-2014
Meningeal inflammation in the form of ectopic lymphoid-like structures has been suggested to play a prominent role development cerebral cortical grey matter pathology multiple sclerosis. The aim this study was analyse incidence and distribution B cell follicle-like an extensive collection cases with secondary progressive sclerosis wide age range determine their relationship diffuse meningeal inflammation, white perivascular infiltrates microglial activation. One hundred twenty three were...
The primary progressive form of multiple sclerosis is characterized by accrual neurological dysfunction from disease onset without remission and it still a matter debate whether this course results different pathogenetic mechanisms compared with secondary sclerosis. Inflammation in the leptomeninges has been identified as key feature may contribute to extensive cortical pathology that accompanies disease. Our aim was investigate extent perivascular meningeal inflammation order understand...
Autologous haematopoietic stem cell transplantation has been tried as one experimental strategy for the treatment of patients with aggressive multiple sclerosis refractory to other immunotherapies. The procedure is aimed at ablating and repopulating immune repertoire by sequentially mobilizing harvesting cells, administering an immunosuppressive conditioning regimen, re-infusing autologous product. 'Non-myeloablative' regimens achieve lymphocytic ablation without marrow suppression have...
Aims Multiple sclerosis ( MS ) is a progressive inflammatory neurological disease affecting myelin, neurons and glia. Demyelination neurodegeneration of cortical grey matter contribute to more severe disease, inflammation the forebrain meninges associates with pathology underlying neocortical matter, particularly in deep sulci. We assessed extent meningeal cerebellum, another structure deeply folded anatomy, better understand association between subarachnoid . Methods examined demyelinating...
Indices of brain volume [grey matter, white matter (WM), lesions] are being used as outcomes in clinical trials patients with multiple sclerosis (MS). We investigated the relationship between cortical volume, number neocortical neurons estimated using stereology and demyelination.Nine MS seven control hemispheres were dissected into coronal slices. On sections stained for Giemsa, cortex was outlined optical disectors applied systematic uniform random sampling. Neurons counted an oil...
Abstract Preventing chronic disease deterioration is an unmet need in people with multiple sclerosis, where axonal loss considered a key substrate of disability. Clinically, sclerosis often presents as progressive myelopathy. Spinal cord cross‐sectional area (CSA) assessed using MRI predicts increasing disability and has, by inference, been proposed indirect index degeneration. However, the association between CSA loss, their correlation demyelination, have never systematically investigated...
Background— The early components of the classical and lectin complement pathways have been shown to protect low-density lipoprotein receptor–deficient mice ( Ldlr −/− ) from atherogenesis. However, role alternative pathway remained unknown, that was investigated in this study. Methods Results— Mice lacking factor B Bf ), initiator pathway, were crossed with studied under different proatherogenic conditions. There no statistically significant difference lipid profiles or atherosclerotic...
Serum antibodies against the glial potassium channel KIR4.1 are found in a subpopulation of multiple sclerosis (MS) patients. Little is known about expression human normal brain tissue and MS lesions. We analyzed pattern lesions subcortical white matter by immunohistochemistry. Markers related proteins, myelin, inflammatory cells were parallel. expressed oligodendrocytes astrocytes adult brain. In oligodendrocytes, appears as homotetramer channel, homo- heterotetramer channels together with...
Disability in multiple sclerosis (MS) is considered primarily a result of axonal loss. However, correlation with spinal cord cross-sectional area-a predictor disability-is poor, questioning the unique role We investigated degree synaptic loss postmortem cords (18 chronic MS, 8 healthy controls) using immunohistochemistry for synaptophysin and synapsin. Substantial (58-96%) synapses throughout was detected, along moderate (47%) anterior horn neurons, notably demyelinating MS lesions. conclude...
Abstract The lack of biomarkers for an early diagnosis neurodegenerative disorders (NDs) has hampered the development therapeutics whose effect would be enhanced by a timely intervention. Neurofilaments light chain (Nf-L), integral part axonal structure, emerged as robust fluid biomarker fatal like amyotrophic lateral sclerosis (ALS). To facilitate large-scale studies into early-stage neurodegeneration, reduce costs samples collection/processing and cold-chain storage, we describe...
Nano-indentation techniques might be better equipped to assess the heterogeneous material properties of plaques than macroscopic methods but there are no bespoke protocols for this kind testing coronary arteries. Therefore, we developed a measurement protocol extract mechanical from healthy and atherosclerotic artery tissue sections. Young's modulus was derived force-indentation data. Metrics collagen fibre density were extracted same tissue, local co-registered microstructure with robust...
Although the accelerating effect of systemic lupus erythematosus (SLE) on atherosclerosis is well established, underlying mechanisms are unknown. The aim this study was to explore hypothesis that autoimmunity modulates hypercholesterolemia in driving arterial pathologic development.Low-density lipoprotein receptor-deficient (Ldlr(-/-) ) mice were crossed with B6.129-Sle16 (Sle16)-congenic autoimmune obtain Sle16. Ldlr(-/-) mice, which compared and Sle16 control mice. All fed either a low-fat...
Purpose Current MRI techniques cannot reliably assess iron content in white matter due to the confounding diamagnetic effect of myelin. The purpose this study was validate with histology a novel mapping technique that uses temperature dependency paramagnetic susceptibility multiple sclerosis (MS) brains, where has been reported show significant variations content. Methods We investigated post mortem brain tissue from three MS patients and one control subject. Temperature‐dependent...
Purpose Validation of quantitative MR measures for myelin imaging in the postmortem multiple sclerosis spinal cord. Methods Four fixed cord samples were imaged first with a 3T clinical scanner to identify areas interest scanning, and then 7T small bore using multicomponent‐driven equilibrium single‐pulse observation T 1 2 protocol produce apparent proton density, , water, intracellular free‐water fraction maps. After imaging, cords sectioned stained histological markers (hematoxylin eosin,...
An amendment to this paper has been published and can be accessed via a link at the top of paper.
OBJECTIVE: To estimate the total neuronal loss in neocortex of people with MS (pwMS) BACKGROUND: Total is unknown. Accurate quantification cortical neurons important to understand (i) pathophysiology and (ii) vivo substrates such as brain atrophy indices derived from magnetic resonance imaging (MRI) DESIGN/METHODS: Formalin fixed hemispheres three pwMS one reference case were used. Hemispheres dissected into 1.1 cm thick coronal slabs, spatially referenced images obtained each slab at...
OBJECTIVE: To assess the association between demyelination and axonal loss in multiple sclerosis (MS) cortico-spinal tract (CST). BACKGROUND: Limb dysfunction due to damage of (CST) axons is common among people with MS (pwMS). The significance for chronic CST unclear, possibly owing differences sampling techniques used previous studies DESIGN/METHODS: Fixed post mortem SC five pwMS two healthy controls (HC), were sampled at 5mm intervals throughout sections stained myelin basic protein (MBP)...