Abstract
Thrombin and other proteases involved in coagulation also have the potential to stimulate
inflammation in the brain to a large extent through the protease-activated receptors
(PARs). Such exposure of the brain to increased levels of coagulation factors is more
likely to occur during vasculitis and activation of intrinsic coagulation in the brain
and may cause inflammatory diseases such as multiple sclerosis. There is growing evidence
from animal models and human brain samples that links upregulation of coagulation
factors to inflammatory central nervous system (CNS) disease. Evidence includes measures
of thrombin-like activity, levels of its receptors, PARs, and inhibitors of the coagulation
pathway. The major receptor for thrombin, PAR-1, has now been definitively located
to the synapse and node of Ranvier and its excessive activation leads to blocks in
long-term potentiation and in nerve conduction. There is growing evidence that modulating
coagulation in models of CNS inflammatory disease has beneficial clinical effects.
These findings suggest that coagulation-like pathways play a significant role in the
pathogenesis of inflammatory diseases in the CNS and present a viable target for therapeutic
strategies.
Keywords multiple sclerosis - antiphospholipid syndrome - thrombin - synaptic function - conduction
block
