Dose-response, therapeutic time-window and tPA-combinatorial efficacy of compound 21: A randomized, blinded preclinical trial in a rat model of thromboembolic stroke
Dose-response, therapeutic time-window and tPA-combinatorial efficacy of compound 21: A randomized, blinded preclinical trial in a rat model of thromboembolic stroke
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DOI：
10.1177/0271678x18764773
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发表时间：
2019-08-01
影响因子：
6.3
通讯作者：
Fagan, Susan C.
中科院分区：
文献类型：
--
作者：
Ishrat, Tauheed;Fouda, Abdelrahman Y.;Fagan, Susan C.
The aim of this translational, randomized, controlled, blinded preclinical trial was to determine the effect of compound 21 (C21) in embolic stroke.对大鼠进行栓塞大脑中动脉闭塞（eMCAO）。他们接受 C21（0.01、0.03 和 0.06 mg/kg/d）或盐水（口服）五天，第一剂在 eMCAO 后 3 小时静脉注射。对于时间窗研究，C21 的最佳剂量在 eMCAO 后 3、6 或 24 小时开始，并持续五天。 For the combinatorial study, animals received IV-tissue plasminogen activator (tPA) at either 2 or 4 h, with IV-C21 (0.01 mg/kg) or saline at 3 h post-eMCAO and daily thereafter for five days.进行行为测试后，收集大脑进行分析。剂量反应研究表明，最低剂量（0.01 毫克/千克）的 C21 可显着改善运动功能。在时间窗研究中，在 eMCAO 后 6 小时和 24 小时给予相同的剂量会带来改善。此外，接受 C21 治疗的动物在新物体识别测试中表现更好。 Neither the single treatment with C21 or tPA (4 h) nor the combination therapy was effective in reducing the hemorrhage or infarct size, although C21 alone lowered sensorimotor deficit scores post-eMCAO.未来的研究应该关注 C21 的长期认知益处，而不是急性神经保护作用。
The aim of this translational, randomized, controlled, blinded preclinical trial was to determine the effect of compound 21 (C21) in embolic stroke. Rats were subjected to embolic-middle cerebral artery occlusion (eMCAO). They received C21 (0.01, 0.03 and 0.06 mg/kg/d) or saline (orally) for five days, with the first-dose given IV at 3 h post-eMCAO. For the time-window study, the optimal-dose of C21 was initiated at 3, 6 or 24 h post-eMCAO and continued for five days. For the combinatorial study, animals received IV-tissue plasminogen activator (tPA) at either 2 or 4 h, with IV-C21 (0.01 mg/kg) or saline at 3 h post-eMCAO and daily thereafter for five days. After performing the behavior tests, brains were collected for analyses. The dose-response study showed significant motor improvements with the lowest-dose (0.01 mg/kg) of C21. In the time-window study, this same dose resulted in improvements when given 6 h and 24 h post-eMCAO. Moreover, C21-treated animals performed better on the novel object recognition test. Neither the single treatment with C21 or tPA (4 h) nor the combination therapy was effective in reducing the hemorrhage or infarct size, although C21 alone lowered sensorimotor deficit scores post-eMCAO. Future studies should focus on the long-term cognitive benefits of C21, rather than acute neuroprotection.