Summary
The blood coagulation cascade proteolytic enzyme, thrombin, affects many cell types,
including neurons and astrocytes, in which it prevents process outgrowth and induces
significant morphological degeneration and even cell death. Since thrombin may contribute
significantly to pathological conditions in the central nervous system (CNS), where
it is synthesized locally, we measured the levels of thrombin and its precursor, prothrombin,
in the cerebrospinal fluid (CSF) of 67 individuals from 6 groups: non-neurologic controls
(NNC); spinal degenerative disease (SDD); peripheral nerve disease (PND); cerebrovascular,
neuroimmune and seizure disorders and tumor (CNSD); traumatic brain injury (TBI) and
neurodegenerative disorders (NDD). We employed a sensitive chromogenic assay utilizing
the thrombin specific tripeptide substrate, S-2238, to evaluate CSF levels of thrombin
and prothrombin. The latter estimated after its conversion to active enzyme by the
snake venom prothrombinase, ecarin. No measurable active thrombin was detected in
these CSF samples. However, activatable prothrombin was measured in all groups. The
mean activatable prothrombin concentrations (in nM) were 7.26 ± 3.39 (NNC); 8.85 ±
3.09 (SDD); 6.78 ± 2.58 (PND); 6.33 ± 3.87 (CNSD); 5.10 ± 1.86 (TBI), and 7.80 ± 3.27
(NDD). Duncan’s multiple comparison test showed significant reduction (p <0.05) in
prothrombin levels of the TBI group. Our data suggests that the prothrombin zymogen
gains access to the CSF, likely-across either an intact or compromised blood-brain
barrier (BBB), in increased amounts with age. Reduced levels in TBI patients may have
diagnostic and/or prognostic value.
