Enhancing Spinal Plasticity Amplifies the Benefits of Rehabilitative Training and Improves Recovery from Stroke

Enhancing Spinal Plasticity Amplifies the Benefits of Rehabilitative Training and Improves Recovery from Stroke
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DOI:
10.1523/jneurosci.0770-17.2017
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发表时间:
2017-11-08
影响因子:
5.3
通讯作者:
Winship, Ian R.
Winship, Ian R.
中科院分区:
医学1区
文献类型:
--
作者:
Wiersma, Anna M.;Fouad, Karim;Winship, Ian R.

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中风后的有限恢复几乎完全发生在受伤后的第一周。此外,康复训练的功效在这一狭窄的时间范围之外是有限的。对侧损伤脊髓中备用皮质脊髓束轴突的发芽对感觉运动恢复做出了重要贡献,但这种结构可塑性也仅限于中风后的前几周。在这里,我们测试的假设,诱导可塑性的脊髓在慢性中风可以改善恢复持续的感觉运动障碍。我们通过脊柱内注射软骨素酶ABC增强了雄性Sprague-Dawley大鼠在慢性中风期间(初始缺血性损伤后数周)的脊柱可塑性。我们的数据表明,软骨素酶注射到对侧病变的颈脊髓灰质给药后28天中风引起显着发芽的皮质脊髓轴突起源于梗死周围皮层。在慢性中风期间注射软骨素酶ABC而不进行额外训练可导致感觉运动缺陷的中度改善。重要的是,这种疗法大大增强了慢性中风期间在熟练的前肢伸展任务中提供的康复训练的功效。这些新数据表明,慢性中风期间的脊柱治疗可以放大延迟康复训练的益处,并有可能减少中风幸存者的永久性残疾。
The limited recovery that occurs following stroke happens almost entirely in the first weeks postinjury. Moreover, the efficacy of rehabilitative training is limited beyond this narrow time frame. Sprouting of spared corticospinal tract axons in the contralesional spinal cord makes a significant contribution to sensorimotor recovery, but this structural plasticity is also limited to the first few weeks after stroke. Here, we tested the hypothesis that inducing plasticity in the spinal cord during chronic stroke could improve recovery from persistent sensorimotor impairment. We potentiated spinal plasticity during chronic stroke, weeks after the initial ischemic injury, in male Sprague-Dawley rats via intraspinal injections of chondroitinase ABC. Our data show that chondroitinase injections into the contralesional gray matter of the cervical spinal cord administered 28 d after stroke induced significant sprouting of corticospinal axons originating in the peri-infarct cortex. Chondroitinase ABC injection during chronic stroke without additional training resulted in moderate improvements of sensorimotor deficits. Importantly, this therapy dramatically potentiated the efficacy of rehabilitative training delivered during chronic stroke in a skilled forelimb reaching task. These novel data suggest that spinal therapy during chronic stroke can amplify the benefits of delayed rehabilitative training with the potential to reduce permanent disability in stroke survivors.