title: Early detection of thrombin activity in neuroinflammatory disease.
abstract: 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.
authors.affiliation: Gladstone Institute of Neurological Disease, University of California, San Francisco, San Francisco, CA.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Davalos
authors.forename: Kim M
authors.initials: KM
authors.lastname: Baeten
authors.forename: Michael A
authors.initials: MA
authors.lastname: Whitney
authors.forename: Eric S
authors.initials: ES
authors.lastname: Mullins
authors.forename: Beth
authors.initials: B
authors.lastname: Friedman
authors.forename: Emilia S
authors.initials: ES
authors.lastname: Olson
authors.forename: Jae Kyu
authors.initials: JK
authors.lastname: Ryu
authors.forename: Dimitri S
authors.initials: DS
authors.lastname: Smirnoff
authors.forename: Mark A
authors.initials: MA
authors.lastname: Petersen
authors.forename: Catherine
authors.initials: C
authors.lastname: Bedard
authors.forename: Jay L
authors.initials: JL
authors.lastname: Degen
authors.forename: Roger Y
authors.initials: RY
authors.lastname: Tsien
authors.forename: Katerina
authors.initials: K
authors.lastname: Akassoglou
mesh_terms: D000818:Animals; D001369:Axons / Q000473:pathology; D001779:Blood Coagulation Factors / Q000737:chemistry; D000075302:Connexin 30; D017630:Connexins / Q000235:genetics; D003711:Demyelinating Diseases / Q000209:etiology / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D005337:Fibrin / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D004676:Myelin Basic Protein / Q000378:metabolism; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000633:toxicity; D010446:Peptide Fragments / Q000633:toxicity; D011070:Poly I-C / Q000633:toxicity; D013917:Thrombin / Q000737:chemistry / Q000378:metabolism*
chemical_list: D001779:Blood Coagulation Factors; D000075302:Connexin 30; D017630:Connexins; C100629:Gjb6 protein, mouse; D004676:Myelin Basic Protein; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; C445081:myelin oligodendrocyte glycoprotein (35-55); D049452:Green Fluorescent Proteins; D005337:Fibrin; D013917:Thrombin; D011070:Poly I-C
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