Thrombin inhibition by argatroban ameliorates early brain injury and improves neurological outcomes after experimental subarachnoid hemorrhage in rats

Background and Purpose-We investigated the role of thrombin in early brain injury after subarachnoid hemorrhage (SAH). Methods-The standard intravascular perforation model was used to produce experimental SAH in Sprague Dawley rats. Low-dose (0.3 mg/h) and high-dose (0.9 mg/h) argatroban, a direct thrombin inhibitor, were evaluated for effects on brain edema, blood-brain barrier (BBB) disruption, apoptotic cell death, inflammatory marker, and neurological outcomes after SAH. Results-Both doses of argatroban attenuated BBB disruption; however, only high-dose was effective in lowering edema in all brain regions, reducing cell death, and inflammatory marker expression, and improving neurological outcomes. Conclusions-Thrombin inhibition by argatroban improves neurological outcomes and provides neuroprotection against acute events after SAH such as BBB disruption, brain edema, and cell death. © 2009 American Heart Association, Inc.