Wiersma Anna M, Fouad Karim, Winship Ian R
Neuroscience and Mental Health Institute.
Faculty of Rehabilitation Medicine, and.
J Neurosci. 2017 Nov 8;37(45):10983-10997. doi: 10.1523/JNEUROSCI.0770-17.2017. Epub 2017 Oct 12.
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. The brain and spinal cord undergo adaptive rewiring ("plasticity") following stroke. This plasticity allows for partial functional recovery from stroke induced sensorimotor impairments. However, the plasticity that underlies recovery occurs predominantly in the first weeks following stroke, and most stroke survivors are left with permanent disability even after rehabilitation. Using animal models, our data show that removal of plasticity-inhibiting signals in the spinal cord (via intraspinal injections of the enzyme chondroitinase ABC) augments rewiring of circuits connecting the brain to the spinal cord, even weeks after stroke. Moreover, this plasticity can be harnessed by rehabilitative training to significantly promote sensorimotor recovery. Thus, intraspinal therapy may augment rehabilitative training and improve recovery even in individuals living with chronic disability due to stroke.
中风后的有限恢复几乎完全发生在损伤后的头几周。此外，康复训练的效果在这个狭窄的时间框架之外是有限的。对侧脊髓中 spared 皮质脊髓束轴突的发芽对感觉运动恢复有重要贡献，但这种结构可塑性也仅限于中风后的头几周。在这里，我们测试了这样一个假设，即在慢性中风期间诱导脊髓可塑性可以改善持续性感觉运动障碍的恢复。我们通过脊髓内注射软骨素酶 ABC，在雄性 Sprague-Dawley 大鼠的初始缺血性损伤数周后的慢性中风期间增强脊髓可塑性。我们的数据表明，在中风后 28 天向颈脊髓对侧灰质注射软骨素酶可诱导起源于梗死周围皮质的皮质脊髓轴突显著发芽。在慢性中风期间注射软骨素酶 ABC 而不进行额外训练会导致感觉运动缺陷有适度改善。重要的是，这种疗法显著增强了在慢性中风期间进行的熟练前肢伸展任务的康复训练效果。这些新数据表明，慢性中风期间的脊髓治疗可以增强延迟康复训练的益处，有可能减少中风幸存者的永久性残疾。中风后大脑和脊髓会经历适应性重新布线（“可塑性”）。这种可塑性允许从中风引起的感觉运动障碍中部分功能恢复。然而，恢复所基于的可塑性主要发生在中风后的头几周，并且大多数中风幸存者即使经过康复仍会留下永久性残疾。使用动物模型，我们的数据表明，去除脊髓中抑制可塑性的信号（通过脊髓内注射软骨素酶 ABC）可增强连接大脑与脊髓的回路的重新布线，即使在中风数周后也是如此。此外，这种可塑性可以通过康复训练来利用，以显著促进感觉运动恢复。因此，脊髓内治疗可能会增强康复训练，并改善即使是因中风而患有慢性残疾的个体的恢复情况。
