Fasudil, a Rho-kinase inhibitor, attenuates induction and progression of cerebral aneurysms: experimental study in rats using vascular corrosion casts

Neurosci Lett. 2010 Feb 5;470(1):76-80. doi: 10.1016/j.neulet.2009.12.061. Epub 2009 Dec 30.

Abstract

Fasudil (a Rho-kinase inhibitor) has been shown to attenuate abdominal aortic aneurysm development, but any preventive effect against development of cerebral aneurysms is unclear. The effect of fasudil on the development of cerebral aneurysms was investigated in 55 female Sprague-Dawley rats divided into 4 groups: Group 1 (n=10) was the control group without treatment. Groups 2-4 (n=15 each) were subjected to cerebral aneurysm induction procedures plus 1% NaCl in the drinking water. Groups 3 and 4 were also treated with 0.5 or 1.0mg/mL of fasudil in the drinking water, respectively. Vascular corrosion casts of the cerebral arteries were prepared and examined using a scanning electron microscope after 2 months. No significant differences were observed in the degree of induced hypertension between Groups 2, 3 and 4. No aneurysms were found in Group 1. Examination of the left anterior cerebral-olfactory artery junction, which is the most susceptible site for aneurysm development, found significantly fewer aneurysmal lesions in Groups 3 (60%) and 4 (53%) compared to Group 2 (100%) (P<0.02). This study suggests that fasudil attenuated induction of cerebral aneurysms in the rat model.

MeSH terms

  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / administration & dosage
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / analogs & derivatives*
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / pharmacology
  • Animals
  • Brain / blood supply
  • Brain / drug effects
  • Brain / pathology
  • Cerebral Arteries / drug effects
  • Cerebral Arteries / pathology*
  • Cerebral Arteries / ultrastructure
  • Disease Models, Animal
  • Disease Progression
  • Dose-Response Relationship, Drug
  • Female
  • Intracranial Aneurysm / drug therapy*
  • Intracranial Aneurysm / pathology*
  • Microscopy, Electron, Scanning
  • Neuroprotective Agents / administration & dosage
  • Neuroprotective Agents / pharmacology*
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • rho-Associated Kinases / antagonists & inhibitors

Substances

  • Neuroprotective Agents
  • Protein Kinase Inhibitors
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
  • rho-Associated Kinases
  • fasudil