Effects of thrombin inhibitor on thrombin-related signal transduction and cerebral vasospasm in the rabbit subarachnoid hemorrhage model

Thrombin is activated in the cerebrospinal fluid (CSF) after a subarachnoid hemorrhage (SAH). However, the relationship between thrombin and cerebral vasospasm has not yet been fully established. The aim of this study was to investigate the possibility of thrombin as a causative factor for cerebral vasospasm and to delineate the signal transduction mechanism that results in thrombin-inducing sustained vasoconstriction in cerebral vasospasm. In the SAH group, SAH was simulated by the 2-hemorrhage rabbit model. In the treatment group, antithrombin III (AT-III) was injected into the cisterna magna just before production of the SAH. CSF samples were obtained serially to measure d-dimer with latex photometric immunoassay. On day 4, the basilar artery was excised after perfusion-fixation. The degree of cerebral vasospasm was evaluated by measuring the cross-sectional area of each basilar arterial lumen, and the expression of mitogen-activated protein kinase (MAPK) in the vascular wall was examined with an immunohistochemical technique. In the treatment group, the value of d-dimer on day 4 was 0.83+/-0.07 microg/mL, which was statistically significantly lower than that in the nontreated SAH group (2.49+/-0.09 microg/mL, P