Chronic electrical stimulation of the intact corticospinal system after unilateral injury restores skilled locomotor control and promotes spinal axon outgrowth.

Chronic electrical stimulation of the intact corticospinal system after unilateral injury restores skilled locomotor control and promotes spinal axon outgrowth.
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DOI:
10.1523/jneurosci.1435-10.2010
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发表时间:
2010-08-11
期刊:
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子:
--
通讯作者:
Martin JH
Martin JH
中科院分区:
其他
文献类型:
--
作者:
Carmel JB;Berrol LJ;Brus-Ramer M;Martin JH

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脑或脊髓损伤通常会保留一些皮质脊髓(CS)连接。这些残留回路自发地发芽,并响应基于活动的治疗。我们假设,增强备用CS回路的活动将恢复损伤后失去的熟练运动控制,并增加脊髓中CS终止的生长。选择性损伤大鼠半侧CS束(CST)后,对备用侧的前肢运动皮层区进行10 d的电刺激,并测试30 d的运动表现。损伤和CST刺激的大鼠在水平梯子上行走时,在熟练的爪子放置方面表现出实质性的改善。到测试期结束时,在损伤和刺激的大鼠中先前受损的前肢的行走错误恢复到基线,而仅在损伤的大鼠中错误仍然升高。尽管所有动物完成任务的时间都恢复了正常,但只有在刺激组中,错误模式才恢复正常。与仅损伤的大鼠相比,电刺激还引起损伤侧同侧脊髓中CST轴突末端的强劲生长。生长的产物是针对同侧CST轴突终端的正常灰质领土。因此,刺激备用CS电路诱导大量轴突生长到脊髓的大部分去神经支配侧,并恢复了以前受损肢体的正常运动控制。
Injury to the brain or spinal cord usually preserves some corticospinal (CS) connections. These residual circuits sprout spontaneously and in response to activity-based treatments. We hypothesized that augmenting activity in spared CS circuits would restore the skilled motor control lost after injury and augment outgrowth of CS terminations in the spinal cord. After selective injury of one half of the CS tract (CST) in the rat, we applied 10 days of electrical stimulation to the forelimb area of motor cortex of the spared half and tested motor performance for 30 days. Rats with injury and CST stimulation showed substantial improvements in skilled paw placement while walking over a horizontal ladder. By the end of the testing period, the walking errors of the previously impaired forelimb in rats with injury and stimulation returned to baseline, while the errors remained elevated in rats with injury only. Whereas the time to perform the task returned to normal in all animals, the pattern of errors returned to normal only in the stimulated group. Electrical stimulation also caused robust outgrowth of CST axon terminations in the ipsilateral spinal cord, the side of impairment, compared with rats with injury only. The outgrowth was directed to the normal gray matter territory of ipsilateral CST axon terminations. Thus, stimulation of spared CS circuits induced substantial axon outgrowth to the largely denervated side of the spinal cord and restored normal motor control in the previously impaired limbs.