Neuroprotection by Intrathecal Application of Liposome-entrapped Fasudil in a Rat Model of Ischemia
スポンサーリンク
概要
- 論文の詳細を見る
Pharmacological treatment for cerebral ischemia cannot attain sufficiently high concentrations of the drugs in the cerebrospinal fluid(CSF)without precipitating systemic side effects. The objective of this study is the development of a liposomal drug delivery system that maintains effective concentrations of protein kinase inhibitors fasudil in the CSF, resulting in neuroprotection against cerebral ischemia. Focal cerebral ischemia in rats was induced by middle cerebral artery occlusion using an intraluminal suture technique. Treated rats received 0.25 mg liposome-entrapped fasudil via the cisterna magna 2 hours after ischemic insult. Control rats received drug-free liposomes. Neurological condition and the infarct size were assessed at 24 and 72 hours after ischemia. The concentration of liposome-entrapped fasudil in the CSF was measured before sacrifice. Treated animals showed significantly improved neurological outcomes after the 24-hour observation period compared to the control group (p<0.001). Treatment with 0.25 mg liposomal fasudil resulted in a reduction in the infarct area (24 hours:29.0 ± 4.4%, 72 hours:28.1 ± 3.9% of total brain slices) compared to controls (49.6 ± 4.6%, p<0.001), but there was no statistical difference between 24 and 72 hours. At 24 hours post-administration, CSF concentrations of liposome-entrapped fasudil were 45.4 ± 31.5 μg/ml (20% of the injected dose). A single intrathecal injection of liposomal fasudil can maintain a therapeutic drug concentration in the CSF over a period of time, significantly decreasing infarct size in a rat model of acute ischemia.
- 日本脳神経外科学会の論文
- 2001-03-15
著者
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Ishida Tatsuhiro
Department of Pharmacokinetics and Biopharmaceutics, Subdivision of Biopharmaceutical Sciences, Inst
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Shuaib Ashfaq
Neurology Division Department Of Medicine University Of Alberta
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TAKANASHI Yoshihiro
Department of Neurosurgery, Yokohama City University School of Medicine
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KIRCHMEIER Marc
Department of Pharmacology, University of Alberta
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ALLEN Theresa
Department of Pharmacology, University of Alberta
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Ishida Tatsuhiro
Department Of Pharmacokinetics And Biopharmaceutics Institute Of Health Biosciences The University O
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Ishida Tatsuhiro
Department Of Pharmacology University Of Alberta
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Allen Theresa
Department Of Pharmacology University Of Alberta
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Kirchmeier Marc
Department Of Pharmacology University Of Alberta
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Takanashi Yoshihiro
Department Of Neurosurgery Yokohama City University School Of Medicine
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Takanashi Yoshihiro
Department of Electronics, Aichi Institute of Technology
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