Abstract W MP96: The Role of Thrombin in Hydrocephalus after Intraventricular Hemorrhage

Abstract

Background: Hydrocephalus after intraventricular hemorrhage (IVH) is a common and major complication that causes clinical deterioration and affects recovery. The mechanisms of hydrocephalus are still not clear. Previous studies demonstrated that thrombin is an important factor in brain injury after intracerebral hemorrhage. This study investigated the effect of thrombin on hydrocephalus development in a rat IVH model. Methods: There were three parts in this study. First, male Sprague-Dawley rats had an injection of 200μl saline, autologous blood or heparinized blood into the right lateral ventricle and had MRI scanning to determine lateral ventricle size at different times up to 4 weeks. Second, rats had an injection of 50μl saline or 3U thrombin into the right lateral ventricle. Third, rats had an injection of thrombin (3U) with a protease-activated receptor-1 (PAR-1) antagonist, SCH79797 (0.15 nmol), or vehicle into the right lateral ventricle. Lateral ventricle volumes were measured by MRI and the brains were used for immunohistochemistry and Western blot analysis at 24 hours. Results: Intraventricular injection of autologous blood induced hydrocephalus from day-1 to -28. Co-injection of heparin with blood resulted in less hydrocephalus at all time points compared with blood injection alone (p<0.05). Intraventricular injection of thrombin, but not saline induced significant hydrocephalus, ventricular wall damage, blood-brain barrier disruption, and PAR-1 upregulation in the periventricular area. Thrombin-induced hydrocephalus was reduced by co-injection of the PAR-1 antagonist SCH79797 (p<0.05). Conclusions: Thrombin contributes to hydrocephalus development after intraventricular hemorrhage and thrombin-induced hydrocephalus is through activation of PAR-1.