High-Intensity Interval Training Improves Physical Function, Prevents Muscle Loss, and Modulates Macrophage-Mediated Inflammation in Skeletal Muscle of Cerebral Ischemic Mice

Although skeletal muscle is the main effector organ largely accounting for disability after stroke, considerably less attention is paid to the secondary abnormalities of stroke-related skeletal muscle loss. It is necessary to explore the mechanism of muscle atrophy after stroke and further develop e...

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Main Authors: Lu Luo, Meixi Liu, Hongyu Xie, Yunhui Fan, Jingjun Zhang, Li Liu, Yun Li, Qiqi Zhang, Junfa Wu, Congyu Jiang, Yi Wu
Format: Article
Language:English
Published: Wiley 2021-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2021/1849428
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author Lu Luo
Meixi Liu
Hongyu Xie
Yunhui Fan
Jingjun Zhang
Li Liu
Yun Li
Qiqi Zhang
Junfa Wu
Congyu Jiang
Yi Wu
author_facet Lu Luo
Meixi Liu
Hongyu Xie
Yunhui Fan
Jingjun Zhang
Li Liu
Yun Li
Qiqi Zhang
Junfa Wu
Congyu Jiang
Yi Wu
author_sort Lu Luo
collection DOAJ
description Although skeletal muscle is the main effector organ largely accounting for disability after stroke, considerably less attention is paid to the secondary abnormalities of stroke-related skeletal muscle loss. It is necessary to explore the mechanism of muscle atrophy after stroke and further develop effective rehabilitation strategy. Here, we evaluated the effects of high-intensity interval (HIIT) versus moderate-intensity aerobic training (MOD) on physical function, muscle mass, and stroke-related gene expression profile of skeletal muscle. After the model of middle cerebral artery occlusion (MCAO) was successfully made, the blood lactate threshold corresponding speed (SLT) and maximum speed (Smax) were measured. Different intensity training protocols (MOD<SLT; SLT<HIIT<Smax) were carried out for 3 weeks beginning at 7 days after MCAO in the MOD and HIIT groups, respectively. We found that both HIIT and MOD prevented stroke-related gastrocnemius muscle mass loss in MCAO mice. HIIT was more beneficial than MOD for improvements in muscle strength, motor coordination, walking competency, and cardiorespiratory fitness. Furthermore, HIIT was superior to MOD in terms of reducing lipid accumulation, levels of IL-1β and IL-6 in paretic gastrocnemius, and improving peripheral blood CD4+/CD8+ T cell ratio, level of IL-10. Additionally, RNA-seq analysis revealed that the differentially expressed genes among HIIT, MOD, and MCAO groups were highly associated with signaling pathways involved in inflammatory response, more specifically the I-kappaB kinase/NF-kappaB signaling. Following the outcome, we further investigated the infiltrating immune cells abundant in paretic muscles. The results showed that HIIT modulated macrophage activation by downregulating CD86+ (M1 type) macrophages and upregulating CD163+ (M2 type) macrophages via inhibiting the TLR4/MyD88/NFκB signaling pathway and exerting an anti-inflammatory effect in paretic skeletal muscle. It is expected that these data will provide novel insights into the mechanisms and potential targets underlying muscle wasting in stroke.
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series Mediators of Inflammation
spelling doaj-art-8fd77f3ee0e2408198b36167f26943d12025-02-03T05:44:38ZengWileyMediators of Inflammation1466-18612021-01-01202110.1155/2021/1849428High-Intensity Interval Training Improves Physical Function, Prevents Muscle Loss, and Modulates Macrophage-Mediated Inflammation in Skeletal Muscle of Cerebral Ischemic MiceLu Luo0Meixi Liu1Hongyu Xie2Yunhui Fan3Jingjun Zhang4Li Liu5Yun Li6Qiqi Zhang7Junfa Wu8Congyu Jiang9Yi Wu10Department of Rehabilitation MedicineDepartment of Rehabilitation MedicineDepartment of Rehabilitation MedicineDepartment of Rehabilitation MedicineDepartment of Rehabilitation MedicineDepartment of Rehabilitation MedicineDepartment of Rehabilitation MedicineDepartment of Rehabilitation MedicineDepartment of Rehabilitation MedicineDepartment of Rehabilitation MedicineDepartment of Rehabilitation MedicineAlthough skeletal muscle is the main effector organ largely accounting for disability after stroke, considerably less attention is paid to the secondary abnormalities of stroke-related skeletal muscle loss. It is necessary to explore the mechanism of muscle atrophy after stroke and further develop effective rehabilitation strategy. Here, we evaluated the effects of high-intensity interval (HIIT) versus moderate-intensity aerobic training (MOD) on physical function, muscle mass, and stroke-related gene expression profile of skeletal muscle. After the model of middle cerebral artery occlusion (MCAO) was successfully made, the blood lactate threshold corresponding speed (SLT) and maximum speed (Smax) were measured. Different intensity training protocols (MOD<SLT; SLT<HIIT<Smax) were carried out for 3 weeks beginning at 7 days after MCAO in the MOD and HIIT groups, respectively. We found that both HIIT and MOD prevented stroke-related gastrocnemius muscle mass loss in MCAO mice. HIIT was more beneficial than MOD for improvements in muscle strength, motor coordination, walking competency, and cardiorespiratory fitness. Furthermore, HIIT was superior to MOD in terms of reducing lipid accumulation, levels of IL-1β and IL-6 in paretic gastrocnemius, and improving peripheral blood CD4+/CD8+ T cell ratio, level of IL-10. Additionally, RNA-seq analysis revealed that the differentially expressed genes among HIIT, MOD, and MCAO groups were highly associated with signaling pathways involved in inflammatory response, more specifically the I-kappaB kinase/NF-kappaB signaling. Following the outcome, we further investigated the infiltrating immune cells abundant in paretic muscles. The results showed that HIIT modulated macrophage activation by downregulating CD86+ (M1 type) macrophages and upregulating CD163+ (M2 type) macrophages via inhibiting the TLR4/MyD88/NFκB signaling pathway and exerting an anti-inflammatory effect in paretic skeletal muscle. It is expected that these data will provide novel insights into the mechanisms and potential targets underlying muscle wasting in stroke.http://dx.doi.org/10.1155/2021/1849428
spellingShingle Lu Luo
Meixi Liu
Hongyu Xie
Yunhui Fan
Jingjun Zhang
Li Liu
Yun Li
Qiqi Zhang
Junfa Wu
Congyu Jiang
Yi Wu
High-Intensity Interval Training Improves Physical Function, Prevents Muscle Loss, and Modulates Macrophage-Mediated Inflammation in Skeletal Muscle of Cerebral Ischemic Mice
Mediators of Inflammation
title High-Intensity Interval Training Improves Physical Function, Prevents Muscle Loss, and Modulates Macrophage-Mediated Inflammation in Skeletal Muscle of Cerebral Ischemic Mice
title_full High-Intensity Interval Training Improves Physical Function, Prevents Muscle Loss, and Modulates Macrophage-Mediated Inflammation in Skeletal Muscle of Cerebral Ischemic Mice
title_fullStr High-Intensity Interval Training Improves Physical Function, Prevents Muscle Loss, and Modulates Macrophage-Mediated Inflammation in Skeletal Muscle of Cerebral Ischemic Mice
title_full_unstemmed High-Intensity Interval Training Improves Physical Function, Prevents Muscle Loss, and Modulates Macrophage-Mediated Inflammation in Skeletal Muscle of Cerebral Ischemic Mice
title_short High-Intensity Interval Training Improves Physical Function, Prevents Muscle Loss, and Modulates Macrophage-Mediated Inflammation in Skeletal Muscle of Cerebral Ischemic Mice
title_sort high intensity interval training improves physical function prevents muscle loss and modulates macrophage mediated inflammation in skeletal muscle of cerebral ischemic mice
url http://dx.doi.org/10.1155/2021/1849428
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