A5018946149- Multiple Sclerosis Research Studies
- Neuroinflammation and Neurodegeneration Mechanisms
- Systemic Sclerosis and Related Diseases
- Peripheral Neuropathies and Disorders
- Systemic Lupus Erythematosus Research
- T-cell and B-cell Immunology
- Alzheimer's disease research and treatments
- Neurological Disease Mechanisms and Treatments
- Reproductive System and Pregnancy
- Acute Ischemic Stroke Management
- Neurogenesis and neuroplasticity mechanisms
- RNA regulation and disease
- Immunotherapy and Immune Responses
- Cytokine Signaling Pathways and Interactions
- Vitamin D Research Studies
- Barrier Structure and Function Studies
- Traumatic Brain Injury and Neurovascular Disturbances
- Tryptophan and brain disorders
- Amyotrophic Lateral Sclerosis Research
- Cerebrovascular and Carotid Artery Diseases
- Immune Response and Inflammation
- Olfactory and Sensory Function Studies
- Ultrasound and Hyperthermia Applications
- Traumatic Brain Injury Research
- Cerebral Venous Sinus Thrombosis
John Radcliffe Hospital
2016-2025
University of Oxford
2016-2025
Vita-Salute San Raffaele University
2024
Istituti di Ricovero e Cura a Carattere Scientifico
2024
NIHR Leeds Musculoskeletal Biomedical Research Unit
2023
Churchill Hospital
2021
New York Hospital Queens
2021
Rush University
2021
Columbia University
2021
NewYork–Presbyterian Hospital
2021
Multiple sclerosis (MS) is a complex trait in which allelic variation the MHC class II region exerts single strongest effect on genetic risk. Epidemiological data MS provide strong evidence that environmental factors act at population level to influence unusual geographical distribution of this disease. Growing implicates sunlight or vitamin D as key factor aetiology. We hypothesised candidate might interact with inherited and sought responsive regulatory elements region. Sequence analysis...
Learning a novel motor skill is associated with well characterized structural and functional plasticity in the rodent cortex. Furthermore, neuroimaging studies of visuomotor learning humans have suggested that can occur white matter (WM), but biological basis for such changes unclear. We assessed influence on WM structure within sensorimotor cortex using both diffusion MRI fractional anisotropy (FA) quantitative immunohistochemistry. Seventy-two adult (male) rats were randomly assigned to...
Conventional magnetic resonance imaging (MRI) of the multiple sclerosis spinal cord is limited by low specificity regarding underlying pathological processes, and new MRI metrics assessing microscopic damage are required. We aim to show for first time that neurite orientation dispersion (i.e., variability in axon/dendrite orientations) a biomarker uncovers previously undetected layers complexity pathology. Also, we validate against histology clinically viable technique measurement (neurite...
Alzheimer's disease (AD) is the most common form of dementia, characterized by progressive cognitive impairment and neurodegeneration. However, despite extensive clinical genomic studies, molecular basis AD development progression remains elusive. To elucidate systems associated with AD, we developed a large scale gene expression dataset from 1053 postmortem brain samples across 19 cortical regions 125 individuals severity spectrum dementia neuropathology AD. We excluded specimens that...
Brain imaging characteristics of MOG antibody disease are largely unknown and it is unclear whether they differ from those multiple sclerosis AQP4 disease. The aim this study was to identify brain discriminators between three inflammatory central nervous system diseases in adults children support diagnostic decisions, drive testing generate mechanism hypotheses. Clinical scans 83 patients with lesions (67 the training 16 validation cohort, 65 18 children) (n = 26), 26) 31) recruited Oxford...
Abstract To match the metabolic demands of brain, mechanisms have evolved to couple neuronal activity vasodilation, thus increasing local cerebral blood flow and delivery oxygen glucose active neurons. Rather than relying on feedback signals such as consumption or glucose, main signalling pathways rely release vasoactive molecules by neurons astrocytes, which act contractile cells. Vascular smooth muscle cells pericytes are associated with arterioles capillaries, respectively, relax induce...
Clinical, imaging, and pathological studies in multiple sclerosis have generally emphasized the relative preservation of axons comparison with myelin. Recent evidence, however, demonstrates that axonal loss is also significant, affects long tracts such as corticospinal sensory relates closely to functional disability. Accordingly, distribution extent this focus current investigation. Post‐mortem material 55 patients 32 matched controls was used examine quantitatively population from medulla...
Multiple sclerosis (MS) is a complex neurological disease. Genetic linkage analysis and genotyping of candidate genes in families with 4 or more affected individuals heavily loaded for susceptibility has not fully explained familial disease clustering.We performed whole exome sequencing to further understand the heightened prevalence MS these families.Forty-three (1 from each family) were sequenced find rare variants genes. On average, >58,000 identified individual. A variant CYP27B1 gene...
The traditional notion that multiple sclerosis is a primary demyelinating disease has led to plaque-centred view of both aetiology and the pathogenesis progression. presence axonal loss received increasing recognition. However, relative roles demyelination have not been fully clarified in nor their possible interrelationships elucidated. Post-mortem material from cerebrum, brainstem spinal cord 55 patients (29 males) with an age range 25-83 years (mean = 57.5 years) length history ranging 2...
Hereditary spastic paraplegia (HSP) comprises a group of inherited neurodegenerative disorders with the shared characteristics progressive weakness and spasticity predominantly affecting lower limbs. Limited pathological accounts have described ‘dying back’ axonal degeneration in this disease. However, distribution extent loss has not been elucidated quantitative way. We studied post‐mortem material from six HSP patients 32 controls detail. The population axons was examined quantitatively...
Multiple sclerosis (MS), a common central nervous system inflammatory disease, has major heritable component. Susceptibility is associated with the MHC class II region, especially HLA-DRB5*0101-HLA-DRB1*1501-HLA-DQA1*0102-HLA-DQB1*0602 haplotypes(hereafter DR2), which dominate genetic contribution to MS risk. Marked linkage disequilibrium (LD) among these loci makes identification of specific locus difficult. The once-leading candidate, HLA-DRB1*15, localizes risk, neutral, and protective...
<h3>Importance</h3> Neuromyelitis optica spectrum disorders (NMOSD) can present with very similar clinical features to multiple sclerosis (MS), but the international diagnostic imaging criteria for MS are not necessarily helpful in distinguishing these two diseases. <h3>Objective</h3> This multicentre study tested previously reported of '(1) at least 1 lesion adjacent body lateral ventricle and inferior temporal lobe; or (2) presence a subcortical U-fibre (3) Dawson9s finger-type lesion' an...
Multiple sclerosis is a chronic inflammatory neurological condition characterized by focal and diffuse neurodegeneration demyelination throughout the central nervous system. Factors influencing progression of pathology are poorly understood. One hypothesis that anatomical connectivity influences spread neurodegeneration. This predicts measures will correlate most strongly between interconnected structures. However, such patterns have been difficult to quantify through post-mortem...
To investigate the relationship among attacks in first 2 years (early relapses), secondary progression (SP), and late disability multiple sclerosis (MS).Cohort study with follow-up of 28 years.Referral MS center.Patients (N=730) relapsing-remitting diagnosed according to Poser criteria, from database London Multiple Sclerosis Clinic, London, Ontario, Canada.Long-term evolution patients high (≥ 3 attacks) early (within disease) frequency relapses. In total SP population grouped by numbers...
Neuronal loss, a key substrate of irreversible disability in multiple sclerosis (MS), is recognized feature MS cortical pathology which the cause remains unknown. Fibrin(ogen) deposition neurotoxic animal models MS, but has not been evaluated human progressive cortex. The aim this study was to investigate extent and distribution fibrin(ogen) cortex elucidate its relationship with neurodegeneration.A postmortem cohort pathologically confirmed (n = 47) control 10) cases used. assessed related...
To investigate the association between neuromyelitis optica spectrum disorder (NMOSD) and pregnancy outcome.An international cohort of women with aquaporin-4 antibody-positive NMOSD ≥1 was studied retrospectively. Multivariate logistic regression used to whether after onset associated an increased risk miscarriage (cohort 40 women) or preeclampsia 57 women).Miscarriage rate higher in pregnancies (42.9% [95% confidence interval 17.7%-71.1%] vs. 7.04% [2.33%-15.7%]). Pregnancies conceived...
Cerebral blood flow (CBF) is important for the maintenance of brain function and its dysregulation has been implicated in Alzheimer's disease (AD). Microglia associations with capillaries suggest they may play a role regulation CBF or blood-brain-barrier (BBB). We explored relationship between microglia pericytes, vessel-resident cell type that major control BBB, discovering spatially distinct subset closely associate pericytes. termed these pericyte-associated (PEM). PEM are present...