Intrathecal application with liposome-entrapped Fasudil for cerebral vasospasm following subarachnoid hemorrhage in rats.
To date, the pharmacological approach to cerebral vasospasm following subarachnoid hemorrhage has been hampered in part by an inability to attain sufficiently high concentrations of vasodilator drugs in the cerebrospinal fluid (CSF). To overcome this limitation of current drug therapy, we have developed a sustained-release preparation of protein kinase inhibitor Fasudil. Cerebral vasospasm in rats was induced by double-injection method. Treated rats received 0.417 mg liposome-entrapped Fasudil via the cisterna magna and control rats received drug-free liposomes in the same manner. The diameter of the basilar artery was assessed at 7 days after the initial blood injection. Vasoconstriction of the rat basilar artery was significantly reduced in group treated with liposomal Fasudil compared to the control group (treated group: 87.7 +/- 6.18%, n= 10; control group: 66.3 +/- 9.82%, n = 10; ***P< 0.001). This new approach for cerebral vasospasm may have significant potential for use in the clinical setting.
Takanashi
Y
Y
Department of Neurosurgery, School of Medicine, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, Japan, 236-0004. ytaka@med.yokohama-cu.ac.jp
Ishida
T
T
Meguro
T
T
Kirchmeier
M J
MJ
Allen
T M
TM
Zhang
J H
JH
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives* / Q000097:blood / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics*; D000818:Animals; D001488:Basilar Artery / Q000187:drug effects / Q000502:physiology; D016503:Drug Delivery Systems / Q000379:methods; D007278:Injections, Spinal; D008081:Liposomes / Q000493:pharmacokinetics; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013345:Subarachnoid Hemorrhage / Q000150:complications*; D014661:Vasoconstriction / Q000187:drug effects; D014665:Vasodilator Agents / Q000097:blood / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics*; D020301:Vasospasm, Intracranial / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control
D008081:Liposomes; D014665:Vasodilator Agents; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C049347:fasudil