Synergistic Neuroprotection by a PAF Antagonist Plus a Docosanoid in Experimental Ischemic Stroke: Dose-Response and Therapeutic Window.
Synergistic Neuroprotection by a PAF Antagonist Plus a Docosanoid in Experimental Ischemic Stroke: Dose-Response and Therapeutic Window.
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PAF拮抗剂以及实验性缺血性中风中的Docosanoid的协同神经保护：剂量反应和治疗窗口。
DOI：
10.1016/j.jstrokecerebrovasdis.2022.106585
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发表时间：
2022-08
影响因子：
2.5
通讯作者：
Bazan, Nicolas G.
中科院分区：
文献类型：
--
作者：
Reid, Madigan M.;Obenaus, Andre;Mukherjee, Pranab K.;Khoutorova, Larissa;Roque, Cassia R.;Petasis, Nicos A.;Oria, Reinaldo B.;Belayev, Ludmila;Bazan, Nicolas G.
我们用LAU-0901(LAU)阻断促炎性血小板激活因子受体(PAFR)，并给予阿司匹林触发的神经保护素D_1(AT-NPD1)，以激活大脑中动脉闭塞(MCAO)后的细胞存活通路，这将导致神经功能的恢复。研究剂量-反应和治疗窗口。雄性SD大鼠给予大鼠大脑中动脉阻塞2小时。进行行为学测试(第1~7天)和第7天的体外MRI检查。在量效关系上，分别给予LAU(45和60 mg/kg；ip)、AT-NPD1(111,222,333μg/kg；iv)、LAU+AT-NPD1(LAU 3h，AT-NPD1 3.15h)或赋形剂。治疗窗分别于MCAO后3h、4h、5h、6h分别给予赋形剂、LAU(60 mg/kg)、AT-NPD1222μg/kg及LAU+AT-NPD1。与赋形剂组相比，LAU和AT-NPD1单独治疗分别改善了40-42%和20-30%的行为，LAU+AT-NPD1治疗改善了40%。与赋形剂相比，所有剂量的LAU和AT-NPD1的T2加权成像(T2WI)体积分别减少了73-90%和67-83%，LAU+AT-NPD1的体积减少了94%。在治疗窗口，当在3、4、5和6小时给予LAU+AT-NPD1时，与赋形剂相比，行为改善了50%、56%、33%和26%，T2WI体积减少了93、90、82和84%。我们在这里首次证明，LAU加AT-NPD1治疗在MCAO中提供了高级别的神经保护，相当于或超过了LAU或AT-NPD1单独提供的中等剂量的神经保护。它有一个宽阔的治疗窗口，可持续到中风发病后6小时。
We tested the hypothesis that blocking pro-inflammatory platelet-activating factor receptor (PAFR) with LAU-0901 (LAU) plus administering a selected docosanoid, aspirin-triggered neuroprotectin D1 (AT-NPD1), which activates cell-survival pathways after middle cerebral artery occlusion (MCAo), would lead to neurological recovery. Dose-response and therapeutic window were investigated. Male SD rats were subjected to 2 hours of MCAo. Behavior testing (days 1–7) and ex vivo MRI on day 7 were conducted. In dose-response, rats were treated with LAU (45 and 60 mg/kg; IP), AT-NPD1 (111, 222, 333 μg/kg; IV), LAU+AT-NPD1 (LAU at 3 hours and AT-NPD1 at 3.15 hours) or vehicle. In the therapeutic window, vehicle, LAU (60 mg/kg), AT-NPD1 (222 μg/kg), and LAU +AT-NPD1 were administered at 3, 4, 5, and 6 hours after onset of MCAo. LAU and AT-NPD1 treatments alone improved behavior by 40–42% and 20–30%, respectively, and LAU+AT-NPD1 by 40% compared to the vehicle group. T2-weighted imaging (T2WI) volumes were reduced with all doses of LAU and AT-NPD1 by 73–90% and 67–83% and LAU+AT-NPD1 by 94% compared to vehicle. In the therapeutic window, LAU+AT-NPD1, when administered at 3, 4, 5, and 6 hours, improved behavior by 50, 56, 33, and 26% and reduced T2WI volumes by 93, 90, 82, and 84% compared to vehicle. We have shown here for the first time that LAU plus AT-NPD1 treatment affords high-grade neuroprotection in MCAo, equaling or exceeding that afforded by LAU or AT-NPD1 alone at consider-ably moderate doses. It has a broad therapeutic window extending to 6 hours after stroke onset.
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DOI：
10.1074/jbc.r117.783076
发表时间：
2017-07-28
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Asatryan A;Bazan NG
通讯作者：
Bazan NG
影响因子：
7.3
作者：
Recchiuti A;Serhan CN
通讯作者：
Serhan CN
影响因子：
62.1
作者：
Serhan, Charles N.;Petasis, Nicos A.
通讯作者：
Petasis, Nicos A.
DOI：
10.1016/j.jstrokecerebrovasdis.2021.105987
发表时间：
2021-07-14
影响因子：
2.5
作者：
Khadankhuu，Bayarmaa;Fei，Yuxiang;Li，Yunman
通讯作者：
Li，Yunman
影响因子：
3.8
作者：
de Brito Toscano, Eliana Cristina;Silva, Bruno Costa;Rachid, Milene Alvarenga
通讯作者：
Rachid, Milene Alvarenga