Journal
ANNALS OF NEUROLOGY
Volume 75, Issue 2, Pages 303-308Publisher
WILEY
DOI: 10.1002/ana.24078
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Funding
- National Multiple Sclerosis Society
- Race to Erase MS
- DoD [W81XWH-05-1-0183 Era]
- NIH National Heart, Lung, and Blood Institute [HL096126]
- NIH National Institute of Neurological Diseases and Stroke [NS027177, NS052189, NS066361]
- March of Dimes [4-FY10-461]
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Although multiple sclerosis (MS) has been associated with the coagulation system, the temporal and spatial regulation of coagulation activity in neuroinflammatory lesions is unknown. Using a novel molecular probe, we characterized the activity pattern of thrombin, the central protease of the coagulation cascade, in experimental autoimmune encephalomyelitis. Thrombin activity preceded onset of neurological signs, increased at disease peak, and correlated with fibrin deposition, microglial activation, demyelination, axonal damage, and clinical severity. Mice with a genetic deficit in prothrombin confirmed the specificity of the thrombin probe. Thrombin activity might be exploited for developing sensitive probes for preclinical detection and monitoring of neuroinflammation and MS progression. Ann Neurol 2014;75:303-308
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