Delayed atomoxetine or fluoxetine treatment coupled with limited voluntary running promotes motor recovery in mice after ischemic stroke.
Delayed atomoxetine or fluoxetine treatment coupled with limited voluntary running promotes motor recovery in mice after ischemic stroke.
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DOI：
10.4103/1673-5374.301031
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发表时间：
2021-07
影响因子：
6.1
通讯作者：
Karamyan VT
中科院分区：
文献类型：
--
作者：
Alamri FF;Al Shoyaib A;Syeara N;Paul A;Jayaraman S;Karamyan ST;Arumugam TV;Karamyan VT
目前，对于促进中风后功能恢复的治疗存在未满足的需求。本研究的目的是评价和比较延迟托莫西汀或氟西汀治疗（从卒中后第5天开始）联合有限的体育锻炼（每天2小时自主轮跑;卒中后第9 - 42天）对光血栓性卒中后成年雄性小鼠运动恢复的剂量依赖性影响。这些药物是选择性去甲肾上腺素或5-羟色胺再摄取抑制剂，适用于与中风无关的疾病。本研究的预定主要终点是在网格行走和圆柱测试中的两个自发运动行为任务中测量的运动功能。此外，我们量化了整个研究中的跑步距离和速度，内侧无颗粒皮质中小白蛋白阳性神经元的数量和梗死体积。这两项感觉运动测试都表明，无论是有限的体育锻炼还是单独的药物治疗，都不能显著促进中风后小鼠的运动恢复。然而，体育锻炼与任何一种药物的结合均可促进中风后第42天运动功能的恢复，其中托莫西汀是一种更有效的药物。这伴随着运动功能恢复的小鼠同侧内侧无颗粒皮质中小清蛋白阳性抑制性中间神经元的显著减少，而实验组之间的梗死体积相当。如果在更大规模的研究中得到进一步验证，我们的观察结果表明，添加托莫西汀或氟西汀治疗加上有限的结构化身体康复可以为难以进行早期高强度物理治疗的卒中幸存者提供治疗方式。此外，根据最近完成的氟西汀在卒中恢复中的评估（AFFINITY）和氟西汀的疗效-卒中随机对照试验（EFFECTS）试验，我们的观察结果要求进行新设计的研究，在这些研究中，氟西汀或托莫西汀药物治疗与结构化的身体康复相结合，而不是单独进行。本研究由德克萨斯理工大学健康科学中心机构动物护理和使用委员会批准（方案编号16019）。
Currently, there is an unmet need for treatments promoting post-stroke functional recovery. The aim of this study was to evaluate and compare the dose-dependent effect of delayed atomoxetine or fluoxetine therapy (starting on post-stroke day 5), coupled with limited physical exercise (2 hours daily voluntary wheel running; post-stroke days 9 to 42), on motor recovery of adult male mice after photothrombotic stroke. These drugs are selective norepinephrine or serotonin reuptake inhibitors indicated for disorders unrelated to stroke. The predetermined primary end-point for this study was motor function measured in two tasks of spontaneous motor behaviors in grid-walking and cylinder tests. Additionally, we quantified the running distance and speed throughout the study, the number of parvalbumin-positive neurons in the medial agranular cortex and infarct volumes. Both sensorimotor tests revealed that neither limited physical exercise nor a drug treatment alone significantly facilitated motor recovery in mice after stroke. However, combination of physical exercise with either of the drugs promoted restoration of motor function by day 42 post-stroke, with atomoxetine being a more potent drug. This was accompanied by a significant decrease in parvalbumin-positive inhibitory interneurons in the ipsilateral medial agranular cortex of mice with recovering motor function, while infarct volumes were comparable among experimental groups. If further validated in larger studies, our observations suggest that add-on atomoxetine or fluoxetine therapy coupled with limited, structured physical rehabilitation could offer therapeutic modality for stroke survivors who have difficulty to engage in early, high-intensity physiotherapy. Furthermore, in light of the recently completed Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) and Efficacy oF Fluoxetine-a randomisEd Controlled Trial in Stroke (EFFECTS) trials, our observations call for newly designed studies where fluoxetine or atomoxetine pharmacotherapy is evaluated in combination with structured physical rehabilitation rather than alone. This study was approved by the Texas Tech University Health Sciences Center Institutional Animal Care and Use Committee (protocol # 16019).
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影响因子：
3.3
作者：
Garcia, C;Chen, MJ;Russo-Neustadt, A
通讯作者：
Russo-Neustadt, A
影响因子：
6.7
作者：
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通讯作者：
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影响因子：
6.9
作者：
Birjandi SZ;Abduljawad N;Nair S;Dehghani M;Suzuki K;Kimura H;Carmichael ST
通讯作者：
Carmichael ST
影响因子：
5.3
作者：
Hu, Qimin;Liu, Lan;Wang, Qiaoshu
通讯作者：
Wang, Qiaoshu
影响因子：
48
作者：
Hankey, Graeme J.;Hackett, Maree L.;Yi, Qilong
通讯作者：
Yi, Qilong