Neuroprotection by intrathecal application of liposome-entrapped fasudil in a rat model of ischemia.
Neuroprotection by intrathecal application of liposome-entrapped fasudil in a rat model of ischemia.
复制标题
在缺血大鼠模型中鞘内应用脂质体包埋的法舒地尔的神经保护作用。
DOI：
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发表时间：
2001
影响因子：
1.9
通讯作者：
Theresa M. Allen
中科院分区：
文献类型：
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作者：
Yoshihiro Takanashi;Tatsuhiro Ishida;M. Kirchmeier;Ashfaq Shuaib;Theresa M. Allen
脑缺血的药物治疗不能在脑脊液（CSF）中获得足够高的药物浓度而不引起全身副作用。本研究的目的是开发一种脂质体药物递送系统，该系统可在CSF中维持蛋白激酶抑制剂法舒地尔的有效浓度，从而对脑缺血产生神经保护作用。采用线栓法制作大鼠局灶性脑缺血模型。治疗大鼠接受0.25毫克脂质体包埋法舒地尔通过枕大池缺血损伤后2小时。对照组大鼠接受不含药物的脂质体。在缺血后24和72小时评估神经系统状况和梗死面积。处死前测量CSF中脂质体包埋法舒地尔的浓度。与对照组相比，治疗组动物在24小时观察期后显示出显著改善的神经学结果（p < 0.001）。与对照组（49.6 +/-4.6%，p < 0.001）相比，0.25 mg法舒地尔脂质体治疗导致梗死面积减少（24小时：29.0 +/-4.4%，72小时：28.1 +/- 3.9%），但24小时和72小时之间没有统计学差异。给药后24小时，脂质体包埋法舒地尔的CSF浓度为45.4 +/- 31.5 μ g/ml（注射剂量的20%）。单次鞘内注射法舒地尔脂质体可以在一段时间内维持CSF中的治疗药物浓度，显著降低急性缺血大鼠模型中的梗死面积。
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 micrograms/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.
影响因子：
8.3
作者：
IMAIZUMI, S;WOOLWORTH, V;CHAN, PH
通讯作者：
CHAN, PH
影响因子：
11.2
作者：
S. Kim;S. Khatibi;Stephen B. Howell;C. McCully;F. Balis;D. Poplack
通讯作者：
S. Kim;S. Khatibi;Stephen B. Howell;C. McCully;F. Balis;D. Poplack