Motor cortex electrical stimulation augments sprouting of the corticospinal tract and promotes recovery of motor function.

Motor cortex electrical stimulation augments sprouting of the corticospinal tract and promotes recovery of motor function.
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DOI:
10.3389/fnint.2014.00051
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发表时间:
2014
影响因子:
3.5
通讯作者:
Martin JH
Martin JH
中科院分区:
医学3区
文献类型:
--
作者:
Carmel JB;Martin JH

文献摘要

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皮质脊髓系统及其直接的脊髓通路--皮质脊髓束(CST)--是控制自主运动的主要系统。我们对成年动物损伤后CST修复的方法是从我们的发现得到启发的,我们的发现是在出生后发育期间,活动推动与脊髓回路建立联系。成熟期不完全损伤后,备用CST环路萌发,部分恢复失去的功能。我们的方法利用活性来增强这种依赖于损伤的CST萌发并促进功能。损伤的延髓锥体单边消除所有的CST轴突从一个半球,并允许检查的CST发芽从未受影响的半球。我们发现,对备用的CST或运动皮质进行10天的电刺激,可以诱导CST轴突萌发,部分重建丢失的CST。刺激还会导致皮质投射到红核的大细胞红核的萌发,红核是红髓束的起始处。CST和向红核的皮质投射的协调生长可以支持运动系统与失神经的脊髓运动神经回路的部分重建。在我们的动物模型中,刺激可以恢复熟练的运动功能。在水平阶梯任务中,受损动物与锥体切开相反,有持续性的前肢缺陷。在急性或慢性损伤后接受运动皮质刺激的大鼠显示出显著的功能改善,将错误率带到了损伤前的对照水平。受刺激的运动皮质的可逆性失活恢复了损伤,证明了受刺激系统对恢复的重要性。运动皮质电刺激是促进备用CST轴突喷出的有效途径。通过优化动物中依赖活动的发芽,我们可以有一种方法,可以在最小延迟的情况下转换到人类进行评估。
The corticospinal system—with its direct spinal pathway, the corticospinal tract (CST) – is the primary system for controlling voluntary movement. Our approach to CST repair after injury in mature animals was informed by our finding that activity drives establishment of connections with spinal cord circuits during postnatal development. After incomplete injury in maturity, spared CST circuits sprout, and partially restore lost function. Our approach harnesses activity to augment this injury-dependent CST sprouting and to promote function. Lesion of the medullary pyramid unilaterally eliminates all CST axons from one hemisphere and allows examination of CST sprouting from the unaffected hemisphere. We discovered that 10 days of electrical stimulation of either the spared CST or motor cortex induces CST axon sprouting that partially reconstructs the lost CST. Stimulation also leads to sprouting of the cortical projection to the magnocellular red nucleus, where the rubrospinal tract originates. Coordinated outgrowth of the CST and cortical projections to the red nucleus could support partial re-establishment of motor systems connections to the denervated spinal motor circuits. Stimulation restores skilled motor function in our animal model. Lesioned animals have a persistent forelimb deficit contralateral to pyramidotomy in the horizontal ladder task. Rats that received motor cortex stimulation either after acute or chronic injury showed a significant functional improvement that brought error rate to pre-lesion control levels. Reversible inactivation of the stimulated motor cortex reinstated the impairment demonstrating the importance of the stimulated system to recovery. Motor cortex electrical stimulation is an effective approach to promote spouting of spared CST axons. By optimizing activity-dependent sprouting in animals, we could have an approach that can be translated to the human for evaluation with minimal delay.