A5010152664- Neuroinflammation and Neurodegeneration Mechanisms
- Cell Adhesion Molecules Research
- Blood properties and coagulation
- Blood Coagulation and Thrombosis Mechanisms
- Protease and Inhibitor Mechanisms
- Immune cells in cancer
- Hemodynamic Monitoring and Therapy
- Tryptophan and brain disorders
- Inflammation biomarkers and pathways
- Medicinal Plants and Bioactive Compounds
- Advanced Glycation End Products research
- Acute Ischemic Stroke Management
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- S100 Proteins and Annexins
- Ocular Surface and Contact Lens
- Ferroptosis and cancer prognosis
- Atherosclerosis and Cardiovascular Diseases
- Hereditary Neurological Disorders
- Alzheimer's disease research and treatments
- Multiple Sclerosis Research Studies
- Lipoproteins and Cardiovascular Health
- Barrier Structure and Function Studies
University of Aberdeen
2010-2021
Gladstone Institutes
2011-2020
University of California, San Francisco
2011-2015
Institute of Medical Sciences
2010
Blood-brain barrier disruption, microglial activation and neurodegeneration are hallmarks of multiple sclerosis. However, the initial triggers that activate innate immune responses their role in axonal damage remain unknown. Here we show blood protein fibrinogen induces rapid toward vasculature is required for neuroinflammation. Using vivo two-photon microscopy, demonstrate microglia form perivascular clusters before myelin loss or paralysis onset that, plasma proteins, specifically...
Abstract Autoimmunity and macrophage recruitment into the central nervous system (CNS) are critical determinants of neuroinflammatory diseases. However, mechanisms that drive immunological responses targeted to CNS remain largely unknown. Here we show fibrinogen, a blood coagulation protein deposited in after blood–brain barrier disruption, induces encephalitogenic adaptive immune peripheral leading demyelination. Fibrinogen stimulates unique transcriptional signature CD11b +...
Although multiple sclerosis (MS) has been associated with the coagulation system, temporal and spatial regulation of activity in neuroinflammatory lesions is unknown. Using a novel molecular probe, we characterized pattern thrombin, central protease cascade, experimental autoimmune encephalomyelitis. Thrombin preceded onset neurological signs, increased at disease peak, correlated fibrin deposition, microglial activation, demyelination, axonal damage, clinical severity. Mice genetic deficit...
The resolution of arterial thrombi is critically dependent on the endogenous fibrinolytic system. Using well-established and complementary whole blood models, we investigated potential tissue-type plasminogen activator (tPA) intra-thrombus distribution proteins, formed ex vivo under shear. tPA was present at physiologically relevant concentrations fibrinolysis monitored using an FITC-labelled fibrinogen tracer. Thrombi were from anticoagulated a Chandler Loop non-anticoagulated perfused over...
Abstract Hypoxia-like tissue alterations, characterized by the upregulation of hypoxia-inducible factor-1α (HIF-1α), have been described in normal appearing white matter and pre-demyelinating lesions multiple sclerosis (MS) patients. As HIF-1α regulates transcription a wide set genes involved neuroprotection neuroinflammation, expression may contribute to pathogenesis inflammatory demyelination. To test this hypothesis, we analyzed effect cell-specific genetic ablation or overexpression on...