Early detection of thrombin activity in neuroinflammatory disease

Ann Neurol. 2014 Feb;75(2):303-8. doi: 10.1002/ana.24078. Epub 2014 Feb 24.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Axons / pathology
  • Blood Coagulation Factors / chemistry
  • Connexin 30
  • Connexins / genetics
  • Demyelinating Diseases / etiology
  • Demyelinating Diseases / pathology
  • Disease Models, Animal
  • Disease Progression
  • Encephalomyelitis, Autoimmune, Experimental / chemically induced
  • Encephalomyelitis, Autoimmune, Experimental / metabolism*
  • Encephalomyelitis, Autoimmune, Experimental / pathology*
  • Fibrin / metabolism
  • Green Fluorescent Proteins / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Myelin Basic Protein / metabolism
  • Myelin-Oligodendrocyte Glycoprotein / toxicity
  • Peptide Fragments / toxicity
  • Poly I-C / toxicity
  • Thrombin / chemistry
  • Thrombin / metabolism*

Substances

  • Blood Coagulation Factors
  • Connexin 30
  • Connexins
  • Gjb6 protein, mouse
  • Myelin Basic Protein
  • Myelin-Oligodendrocyte Glycoprotein
  • Peptide Fragments
  • myelin oligodendrocyte glycoprotein (35-55)
  • Green Fluorescent Proteins
  • Fibrin
  • Thrombin
  • Poly I-C