Hydrocephalus after intraventricular hemorrhage: the role of thrombin

J Cereb Blood Flow Metab. 2014 Mar;34(3):489-94. doi: 10.1038/jcbfm.2013.225. Epub 2013 Dec 11.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Blood-Brain Barrier / drug effects
  • Blood-Brain Barrier / metabolism
  • Blood-Brain Barrier / pathology
  • Cerebral Hemorrhage / complications
  • Cerebral Hemorrhage / metabolism*
  • Cerebral Hemorrhage / pathology
  • Cerebral Ventricles / drug effects
  • Cerebral Ventricles / metabolism*
  • Cerebral Ventricles / pathology
  • Hydrocephalus / etiology
  • Hydrocephalus / metabolism*
  • Hydrocephalus / pathology
  • Injections, Intraventricular
  • Magnetic Resonance Imaging
  • Male
  • Pyrroles / administration & dosage
  • Pyrroles / pharmacology
  • Quinazolines / administration & dosage
  • Quinazolines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, PAR-1 / antagonists & inhibitors
  • Thrombin / administration & dosage
  • Thrombin / metabolism*
  • Thrombin / pharmacology


  • N3-cyclopropyl-7-((4-(1-methylethyl)phenyl)methyl)-7H-pyrrolo(3, 2-f)quinazoline-1,3-diamine
  • Pyrroles
  • Quinazolines
  • Receptor, PAR-1
  • Thrombin