Effects of Subdural Monopolar Cortical Stimulation Paired With Rehabilitative Training on Behavioral and Neurophysiological Recovery After Cortical Ischemic Stroke in Adult Squirrel Monkeys.
Effects of Subdural Monopolar Cortical Stimulation Paired With Rehabilitative Training on Behavioral and Neurophysiological Recovery After Cortical Ischemic Stroke in Adult Squirrel Monkeys.
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DOI：
10.1177/1545968315619701
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发表时间：
2016-02
影响因子：
4.2
通讯作者：
Nudo RJ
中科院分区：
文献类型：
--
作者：
Plautz EJ;Barbay S;Frost SB;Zoubina EV;Stowe AM;Dancause N;Eisner-Janowicz I;Bury SD;Taylor MD;Nudo RJ
皮质刺激（CS）结合康复训练（RT）已被证明对促进大鼠中风后功能恢复有效，但人体临床试验结果好坏参半。评估CS/RT与RT在非人灵长类动物皮质缺血性中风模型中的疗效。松鼠猴学习了一个颗粒检索任务，然后接受了一个梗死的远端前肢（DFL）代表的初级运动皮层。在背侧运动前区皮质（PMD）的备用DFL代表处植入硬膜下单极电极。梗塞后7周，猴接受4-6周的RT（n=8）或CS/RT（n=7; 100 Hz，阴极电流）治疗。在梗死前和梗死后、治疗前、治疗后1周和12周（随访）评估行为表现。主要结局指标是治疗后1周的运动表现。次要结局包括12周时的随访表现和备用DFL表示的神经生理学图的治疗相关变化。虽然在所有猴子中发现了梗死后表现缺陷，但两组表现出相似的恢复特征，RT和CS/RT组之间的运动恢复没有差异。治疗后，RT组PMD DFL面积显著扩大，而CS/RT组则无此变化。运动恢复与运动前区皮层DFL扩张有显著相关性。结果表明，这里使用的特定参数不是最佳的促进非人灵长类动物的行为恢复。尽管CS/RT在大鼠卒中模型中一直显示出有效性，但目前的发现对CS/RT治疗向临床人群的转化具有警示意义。
Cortical stimulation (CS) combined with rehabilitative training (RT) has proven effective for enhancing post-stroke functional recovery in rats, but human clinical trials have had mixed outcomes. To assess the efficacy of CS/RT versus RT in a non-human primate model of cortical ischemic stroke. Squirrel monkeys learned a pellet retrieval task, then received an infarct to the distal forelimb (DFL) representation of primary motor cortex. A subdural monopolar electrode was implanted over the spared DFL representation in dorsal premotor cortex (PMD). Seven weeks post-infarct, monkeys underwent 4-6 weeks of RT (n=8) or CS/RT (n=7; 100 Hz, cathodal current) therapy. Behavioral performance was assessed before and after infarct, prior to therapy, and 1 and 12 weeks post-therapy (follow-up). The primary outcome measure was motor performance at 1 week post-therapy. Secondary outcomes included follow-up performance at 12 weeks and treatment-related changes in neurophysiological maps of spared DFL representations. While post-infarct performance deficits were found in all monkeys, both groups demonstrated similar recovery profiles, with no difference in motor recovery between the RT and CS/RT groups. Post-therapy, PMD DFL area was significantly expanded in the RT group but not the CS/RT group. A significant relationship was found between motor recovery and DFL expansion in premotor cortex. Results suggest that the specific parameters utilized here were not optimal for promoting behavioral recovery in non-human primates. Though CS/RT has consistently shown efficacy in rat stroke models, the present finding has cautionary implications for translation of CS/RT therapy to clinical populations.