Johns Hopkins University, Baltimore, MD, USA.
Ever Neuro Pharma GmbH, Unterach, Oberösterreich, Austria.
Neurorehabil Neural Repair. 2021 Jun;35(6):525-533. doi: 10.1177/15459683211000734. Epub 2021 May 6.
Motor recovery after stroke in humans and in rodent models is time sensitive. Recovery in patients is a result of biological spontaneous recovery via endogenous repair mechanisms and is likely improved by enhancing the synaptic plasticity required for endogenous repair. Cerebrolysin is a polypeptide preparation known to enhance neuroplasticity and may improve recovery in patients. In mice, we tested the hypothesis that Cerebrolysin can act poststroke to enhance both spontaneous and training-associated motor recovery.
Mice were trained to perform a skilled prehension task. We then induced a photothrombotic stroke in the caudal forelimb area, after which we retrained animals on the prehension task in the presence or absence of Cerebrolysin after a 2-day or 8-day delay. Mice received daily intraperitoneal Cerebrolysin or saline injections starting poststroke day 1 or poststroke day 7.
Prior studies showed that poststroke recovery of prehension can occur if animals receive rehabilitative training during an early sensitive period but is incomplete if rehabilitative training is delayed. In contrast, we show complete recovery of prehension, despite a delay in rehabilitative training, when mice receive daily Cerebrolysin administration starting on poststroke day 1 or on poststroke day 8. When Cerebrolysin is given on poststroke day 1, recovery occurred even in the absence of training. Stroke volumes were similar across groups.
Poststroke Cerebrolysin administration leads to recovery of motor function independent of rehabilitative training without a protective effect on stroke volume. This is one of the first demonstrations of training-independent motor recovery in rodent stroke models.
人类和啮齿动物模型中风后的运动功能恢复是时间敏感的。患者的恢复是通过内源性修复机制的生物自发恢复产生的，通过增强内源性修复所需的突触可塑性，可能会改善恢复。脑活素是一种已知可增强神经可塑性的多肽制剂，可能会改善患者的恢复。在小鼠中，我们测试了脑活素可以在中风后发挥作用以增强自发和训练相关的运动恢复的假设。
我们训练小鼠执行熟练的抓握任务。然后，在尾部前肢区诱导光血栓性中风，在 2 天或 8 天后，在存在或不存在脑活素的情况下，我们在抓握任务上重新训练动物。小鼠在中风后第 1 天或第 7 天开始接受每日腹腔内脑活素或盐水注射。
先前的研究表明，如果动物在早期敏感期间接受康复训练，中风后抓握的恢复是可能的，但如果康复训练延迟，则恢复不完全。相比之下，尽管康复训练延迟，我们显示出每日脑活素给药开始于中风后第 1 天或第 8 天的小鼠完全恢复抓握。当脑活素在中风后第 1 天给药时，即使没有训练，也会发生恢复。各组的中风体积相似。
中风后给予脑活素可导致运动功能恢复，而无需康复训练，对中风体积没有保护作用。这是啮齿动物中风模型中首次证明训练独立的运动恢复之一。
