THROMBIN AND ITS PRECURSOR IN HUMAN CEREBROSPINAL-FLUID

The blood coagulation cascade proteolytic enzyme, thrombin, affects ma ny cell types, including neurons and astrocytes, in which it prevents process outgrowth and induces significant morphological degeneration a nd even cell death. Since thrombin may contribute significantly to pat hological conditions in the central nervous system (CNS), where it is synthesized locally, we measured the levels of thrombin and its precur sor, prothrombin, in the cerebrospinal fluid (CSF) of 67 individuals f rom 6 groups: non-neurologic controls (NNC); spinal degenerative disea se (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 chromog enic assay utilizing the thrombin specific tripeptide substrate, S-223 8, to evaluate CSF levels of thrombin and prothrombin. The latter esti mated after its conversion to active enzyme by the snake venom prothro mbinase, ecarin. No measurable active thrombin was detected in these C SF samples. However, activatable prothrombin was measured in all group s. 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 multip le comparison test showed significant reduction (p <0.05) in prothromb in levels of the TBI group. Our data suggests that the prothrombin zym ogen gains access to the CSF, likely across either an intact or compro mised blood-brain barrier (BBB), in increased amounts with age. Reduce d levels in TBI patients may have diagnostic and/or prognostic value.