Wang Dong, Li Lijuan, Pan Hongxia, Huang Liyi, Sun Xin, He Chengqi, Wei Quan
Rehabilitation Medicine Center and Institute of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu 611135, China.
Key Laboratory of Rehabilitation Medicine in Sichuan Province, Sichuan University, Chengdu 611135, China.
Brain Sci. 2022 Dec 20;13(1):4. doi: 10.3390/brainsci13010004.
Most conventional post-stroke rehabilitation treatments do not involve imposed constraints of the unaffected limb. In contrast, Constraint-Induced Movement Therapy (CIMT) is comprised of massed task practice with the affected limb and constraint of the unaffected limb. CIMT is a promising rehabilitation technique used for motor recovery of affected limbs after stroke, but its effectiveness and mechanism are not fully understood. We compared the effects of the two exercise modes on limb function post-stroke in animal models and human subjects, and investigated whether oxidative stress response was involved in regulating the effects. We first conducted a randomized controlled trial (RCT), in which 84 subjects with cerebral infarction were assigned to dose-matched constraint-induced movement therapy (CIMT), or unconstraint exercise (UE), or conventional rehabilitation treatment. Motor functions of the limb are primary outcomes of the RCT measured using Brief Fugl-Meyer upper extremity score (FMA-UE), Ashworth score, and Barthel scale. Psychological influence of CIMT and UE was also examined using Self-Rating Depression Scale (SDS). Next, we investigated the effects of CIMT and UE in rats undergoing middle cerebral artery occlusion and reperfusion (MCAO/R). Motor function, infarct volume, and pathohistological changes were investigated by mNSS, MRI, and histological studies. The role of Keap1-Nrf2-ARE was investigated using qRT-PCR, Western blot, immunochemistry, immunofluorescence, and ELISA experiments. In RCT, patients taking CIMT had a higher score in FMA-UE, Barthel index, and SDS, and a lower score in modified Ashworth, compared to those taking UE. In rats receiving CIMT, motor function was increased, and infarct volume was decreased compared to those receiving UE. The expression of Keap1 protein and mRNA in the peri-infarct tissue was decreased, and Nrf2 and ARE protein and mRNA were increased in rats receiving CIMT compared with UE. Nrf2 agonist t-BHQ increased the benefits of CIMT. In conclusion, CIMT is more effective than UE in improving upper limb motor function, reducing muscle spasm in patients with cerebral infarction compared to UE, but patients receiving CIMT may feel depressed. Moreover, both CIMT and UE are beneficial to limb function recovery and limit the infarct expansion in MCAO/R rats, but CIMT was more effective than UE. Oxidative stress reaction has an essential role in regulating the CIMT induced benefits.
大多数传统的中风后康复治疗并不涉及对未受影响肢体施加限制。相比之下，强制性运动疗法（CIMT）包括对受影响肢体进行大量的任务练习以及对未受影响肢体进行限制。CIMT是一种用于中风后受影响肢体运动恢复的有前景的康复技术，但其有效性和机制尚未完全了解。我们比较了这两种运动模式对动物模型和人类受试者中风后肢体功能的影响，并研究了氧化应激反应是否参与调节这些影响。我们首先进行了一项随机对照试验（RCT），将84名脑梗死患者分为剂量匹配的强制性运动疗法（CIMT）组、无限制运动（UE）组或传统康复治疗组。肢体的运动功能是该RCT的主要结局指标，使用简易Fugl-Meyer上肢评分（FMA-UE）、Ashworth评分和Barthel量表进行测量。还使用自评抑郁量表（SDS）检查了CIMT和UE的心理影响。接下来，我们研究了CIMT和UE对大脑中动脉闭塞再灌注（MCAO/R）大鼠的影响。通过mNSS、MRI和组织学研究来研究运动功能、梗死体积和病理组织学变化。使用qRT-PCR、蛋白质印迹、免疫化学、免疫荧光和ELISA实验研究Keap1-Nrf2-ARE的作用。在RCT中，与接受UE的患者相比，接受CIMT的患者在FMA-UE、Barthel指数和SDS上得分更高，在改良Ashworth评分上得分更低。与接受UE的大鼠相比，接受CIMT的大鼠运动功能增强，梗死体积减小。与UE相比，接受CIMT的大鼠梗死周围组织中Keap1蛋白和mRNA的表达降低，Nrf2和ARE蛋白及mRNA增加。Nrf2激动剂叔丁基对苯二酚增强了CIMT的益处。总之，与UE相比，CIMT在改善脑梗死患者上肢运动功能、减轻肌肉痉挛方面更有效，但接受CIMT的患者可能会感到抑郁。此外，CIMT和UE都有利于肢体功能恢复并限制MCAO/R大鼠的梗死扩展，但CIMT比UE更有效。氧化应激反应在调节CIMT诱导的益处中起重要作用。
