Effects of Thrombin Inhibitor on Thrombin-Related Signal Transduction and Cerebral Vasospasm in the Rabbit

Background and Purpose—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. Methods—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. Results—In the treatment group, the value of D-dimer on day 4 was 0.830.07 g/mL, which was statistically significantly lower than that in the nontreated SAH group (2.490.09 g/mL, P0.01). The cross-sectional area of the arterial lumen in the treatment group was 3.671051.58104 square pixels, which was statistically significantly larger than that in the nontreated SAH group (2.601052.29104 square pixels; P0.01). MAPK was detected diffusely in the vascular smooth muscle cell layer in the nontreated SAH group, but it was absent in the treatment group