Fasudil, a Rho-kinase inhibitor, attenuates induction and progression of cerebral aneurysms: experimental study in rats using vascular corrosion casts.
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.
Eldawoody
Hany
H
Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, 980-8574, Japan. hanyeldawoody@yahoo.com
Shimizu
Hiroaki
H
Kimura
Naoto
N
Saito
Atsushi
A
Nakayama
Toshio
T
Takahashi
Akira
A
Tominaga
Teiji
T
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D002536:Cerebral Arteries / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D004195:Disease Models, Animal; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005260:Female; D002532:Intracranial Aneurysm / Q000188:drug therapy* / Q000473:pathology*; D008855:Microscopy, Electron, Scanning; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors
D018696:Neuroprotective Agents; D047428:Protein Kinase Inhibitors; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D054460:rho-Associated Kinases; C049347:fasudil