Progressive neurological damage after brain or spinal cord trauma causes loss of motor
function and treatment is very limited. Clotting and hemorrhage occur early after spinal cord (SCI)
and traumatic brain injury (TBI), inducing aggressive immune cell activation and progressive neuronal
damage. Thrombotic and thrombolytic proteases have direct effects on neurons and glia, both
healing and also damaging bidirectional immune cell interactions. Serine proteases in the thrombolytic
cascade, tissue- and urokinase-type plasminogen activators (tPA and uPA), as well as the clotting
factor thrombin, have varied effects, increasing neuron and glial cell growth and migration
(tPA), or conversely causing apoptosis (thrombin) and activating inflammatory cell responses. tPA
and uPA activate plasmin and matrix metalloproteinases (MMPs) that break down connective tissue
allowing immune cell invasion, promoting neurite outgrowth. Serine proteases also activate chemokines.
Chemokines are small proteins that direct immune cell invasion but also mediate neuron and
glial cell communication. We are investigating a new class of therapeutics, virus-derived immune
modulators; One that targets coagulation pathway serine proteases and a second that inhibits chemokines.
We have demonstrated that local infusion of these biologics after SCI reduces inflammation
providing early improved motor function. Serp-1 is a Myxomavirus-derived serine protease inhibitor,
a serpin, that inhibits both thrombotic and thrombolytic proteases. M-T7 is a virus-derived
Here we review the roles of thrombotic and thrombolytic serine proteases and chemoattractant proteins,
chemokines, as potential therapeutic targets for SCI. We discuss virus-derived immune modulators
as treatments to reduce progressive inflammation and ongoing nerve damage after SCI.