title: Hydrocephalus after intraventricular hemorrhage: the role of thrombin.
abstract: 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 intraventricular hemorrhage (IVH) model. There were three parts in this study. First, male Sprague-Dawley rats had an injection of 200 μL saline, autologous blood or heparinized blood, into the right lateral ventricle. Second, rats had an injection of 50 μL 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 magnetic resonance imaging and the brains were used for immunohistochemistry and western blot analyses. Intraventricular injection of autologous blood induced hydrocephalus from day 1 to 28. Heparinized blood injection resulted in less hydrocephalus at all time points compared with blood injection alone (P<0.05). Intraventricular injection of thrombin caused significant hydrocephalus, ventricular wall damage, and periventricular blood-brain barrier disruption. Thrombin-induced hydrocephalus was reduced by co-injection of the PAR-1 antagonist SCH79797 (P<0.05). In conclusion, thrombin contributes to hydrocephalus development after IVH and thrombin-induced hydrocephalus is through PAR-1.
authors: Department of Neurosurgery, University of Michigan, Ann Arbor, Michigan, USA.
authors: Feng
authors: F
authors: Gao
authors: Department of Neurosurgery, University of Michigan, Ann Arbor, Michigan, USA.
authors: Fuyi
authors: F
authors: Liu
authors: Department of Neurosurgery, University of Michigan, Ann Arbor, Michigan, USA.
authors: Zhi
authors: Z
authors: Chen
authors: Department of Neurosurgery, University of Michigan, Ann Arbor, Michigan, USA.
authors: Ya
authors: Y
authors: Hua
authors: Department of Neurosurgery, University of Michigan, Ann Arbor, Michigan, USA.
authors: Richard F
authors: RF
authors: Keep
authors: Department of Neurosurgery, University of Michigan, Ann Arbor, Michigan, USA.
authors: Guohua
authors: G
authors: Xi
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002543:Cerebral Hemorrhage / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D002552:Cerebral Ventricles / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D006849:Hydrocephalus / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D007276:Injections, Intraventricular; D008279:Magnetic Resonance Imaging; D008297:Male; D011758:Pyrroles / Q000008:administration & dosage / Q000494:pharmacology; D011799:Quinazolines / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013917:Thrombin / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D010975:Platelet Aggregation Inhibitors
chemical_list: C415424:N3-cyclopropyl-7-((4-(1-methylethyl)phenyl)methyl)-7H-pyrrolo(3, 2-f)quinazoline-1,3-diamine; D011758:Pyrroles; D011799:Quinazolines; D013917:Thrombin; D010975:Platelet Aggregation Inhibitors