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康复训练与外周刺激相结合可促进缺血性脑卒中后的运动功能恢复。

Rehabilitative training paired with peripheral stimulation promotes motor recovery after ischemic cerebral stroke.

机构信息

Department of Neurosurgery, Affiliated Huashan Hospital, Fudan University, Shanghai, China; National Center for Neurological Disorders, Shanghai, China; Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Shanghai, China; Neurosurgical Institute of Fudan University, Shanghai, China; Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China.

Department of Neurosurgery, Affiliated Huashan Hospital, Fudan University, Shanghai, China; National Center for Neurological Disorders, Shanghai, China; Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Shanghai, China; Neurosurgical Institute of Fudan University, Shanghai, China; Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China.

出版信息

Exp Neurol. 2022 Mar;349:113960. doi: 10.1016/j.expneurol.2021.113960. Epub 2021 Dec 22.

Abstract

Spontaneous recovery of ischemic stroke is very limited and often results in the loss of motor and sensory function. Till now, rehabilitative training is the most widely accepted therapy to improve long-term outcome. However, its effectiveness is often suboptimal, largely due to a sharp decline of neuroplasticity in adults. In this study, we hypothesized that a combination of proprioceptive stimulation and rehabilitative training will promote neuroplasticity and functional recovery post injury. To test this hypothesis, we first established a photothrombotic stroke model that lesions the hindlimb sensorimotor cortex. Next, we demonstrated that injecting Cre-dependent AAV-retro viruses into the dorsal column of PV-Cre mice achieves specific and efficient targeting of proprioceptors. With chemogenetics, this method enables chronic activation of proprioceptors. We then assessed effects of combinatorial treatment on motor and sensory functional recovery. Our results showed that pairing proprioceptive stimulation with rehabilitative training significantly promoted skilled motor, but not tactile sensory functional recovery. This further led to significant improvement when compared to rehabilitation training or proprioceptor stimulation alone. Mechanistically, combinatorial treatment promoted cortical layer V neuronal mTOR activity and sprouting of corticospinal axon into the area where proprioceptive afferents terminate in the denervated side of the spinal cord. Serving as a proof of principle, our study thus provided novel insights into the application of combining proprioceptive stimulation and rehabilitative training to improve functional recovery of ischemic stroke and other traumatic brain or spinal cord injuries.

摘要

中风后的自发恢复非常有限,通常会导致运动和感觉功能丧失。到目前为止,康复训练是改善长期预后最广泛接受的治疗方法。然而,其效果往往并不理想,这主要是由于成年人神经可塑性急剧下降所致。在这项研究中,我们假设本体感觉刺激和康复训练的结合将促进损伤后的神经可塑性和功能恢复。为了验证这一假设,我们首先建立了一种光血栓性中风模型,损伤后肢感觉运动皮层。接下来,我们证明了将 Cre 依赖性 AAV-retro 病毒注射到 PV-Cre 小鼠的背柱中可以实现对本体感受器的特异性和高效靶向。通过化学遗传学,这种方法可以实现本体感受器的慢性激活。然后,我们评估了组合治疗对运动和感觉功能恢复的影响。我们的结果表明,本体感觉刺激与康复训练相结合显著促进了熟练运动功能的恢复,但对触觉感觉功能的恢复没有影响。与康复训练或本体感受器刺激单独使用相比,这进一步导致了显著的改善。从机制上讲,组合治疗促进了皮质 V 层神经元 mTOR 活性和皮质脊髓轴突向支配侧脊髓中本体感觉传入终止区域的发芽。作为一个原理证明,我们的研究为将本体感觉刺激和康复训练相结合,以改善中风和其他创伤性脑或脊髓损伤后的功能恢复提供了新的见解。

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