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Regulatory T (Treg) cells contribute to white matter repair following ischemic stroke, but their limited availability in circulation restricts their therapeutic potential. Exercise, as a non-invasive and effective rehabilitation method, has been shown to restore Treg balance in diseases. This study explores the effects of treadmill training on Treg upregulation and its influence on myelin repair and functional recovery in rats with middle cerebral artery occlusion (MCAO). After four weeks of treadmill training, we analyzed the proportion of Treg cells (Tregs), FOXP3 expression, and oligodendrocyte-related protein levels using flow cytometry, immunofluorescence, and Western blotting. Myelin structure was examined with transmission electron microscopy (TEM), while motor coordination and balance were assessed using the fatigue rotarod and CatWalk analysis systems. To further explore the role of Tregs, the FOXP3 inhibitor P60 was used to inhibit Treg activity. The findings of our study indicate that training on a treadmill supports the maturation of oligodendrocytes, leads to an increase in myelin-associated proteins and the thickness of myelin, and promotes the recovery of motor function. Inhibition of Treg activity diminished these benefits, highlighting Tregs' key role in exercise-induced remyelination. These findings suggest that treadmill training facilitates myelin regeneration and functional recovery by upregulating Tregs, offering potential new strategies for stroke treatment. [ABSTRACT FROM AUTHOR]

Introduction: Parkinson's disease (PD) is characterized by progressive neurodegeneration within the nigrostriatum, leading to motor dysfunction. This systematic review aimed to summarize the effects of various exercise training regimens on protein or gene expression within the nigrostriatum and their role in neuroprotection and motor function improvement in animal models of Parkinson's disease (PD). Methods: PubMed, EMBASE, and Web of Science were searched up to June 2024 and included sixteen studies that adhere to PRISMA guidelines and CAMARADES checklist scores ranging from 4 to 6 out of 10. Various exercise training regimens, administered 5 days per week for 6.5 weeks, were applied to MPTP, 6-OHDA, and PFF-α-synuclein-induced PD animal models. Results: Exercise training was found to downregulate the inflammatory pathway by attenuating α-synuclein aggregation, inhibiting the TLR/MyD88/IκBα signaling cascade and NF-κB phosphorylation, and decreasing pro-inflammatory cytokines IL-1β and TNF-α while increasing anti-inflammatory cytokines IL-10 and TGF-β within the nigrostriatum. It also inhibited the ASC and NLRP3 inflammasome complex and reduced the BAX/ Bcl-2 ratio and caspase-1/3 proteins, thereby decreasing neuronal apoptosis in the nigrostriatum. Exercise training elevated the expression of Pro-BDNF, BDNF, GDNF, TrkB, and Erk1/2, providing neurotrophic support to dopaminergic neurons. Furthermore, it upregulated the dopaminergic signaling pathway by increasing the expression of TH, DAT, PSD-95, and synaptophysin in the nigrostriatum. Discussion: The findings suggested that exercise training downregulated inflammatory and apoptotic pathways while upregulated BDNF/GDNF pathways and dopaminergic signaling within the nigrostriatum. These molecular changes contributed to neuroprotection, reduced dopaminergic neuron loss, and improved motor function in PD animal models. Systematic review registration: CRD42024484537 https://www.crd.york.ac.uk/prospero/#recordDetails. [ABSTRACT FROM AUTHOR]

Introduction: Treadmill training (TT) is a gait training technique that has commonly been used in neurorehabilitation, and has positive effects on gait, mobility, and related outcomes in stroke survivors. Transcranial direct current stimulation (tDCS) is a non-invasive approach for modulating brain cortex excitability. Aim: To evaluate the available scientific evidence on the effects of TT combined with tDCS on mobility, motor performance, balance function, and brain-related outcomes in stroke survivors. Methods: Five databases namely the Cochrane library, PEDro, Web of Science, PubMed, and EMBASE, were searched for relevant studies from inception to March, 2024. Only randomized controlled trials were included, and their methodological quality and risk of bias (ROB) were evaluated using the PEDro scale and Cochrane ROB assessment tool respectively. Qualitative and quantitative syntheses (using fixed effects meta-analysis) were employed to analyze the data. Results: The results revealed that TT combined with active tDCS had significant beneficial effects on some mobility parameters, some gait spatiotemporal parameters, some gait kinematic parameters, gait endurance, gait ability, and corticomotor excitability in stroke survivors, but no significant difference on gait speed (P > 0.05), functional mobility (P > 0.05), motor performance (P > 0.05), or some balance functions (P > 0.05), compared with the control conditions. Conclusions: TT combined with active tDCS significantly improves some gait/mobility outcomes and corticomotor excitability in stroke survivors. [ABSTRACT FROM AUTHOR]

Abstract Dual cognitive-walking treadmill training (DTT), designed to replicate real-life walking conditions, has shown promise effect in individuals with Parkinson’s disease (PD). This study aims to compare the effects of DTT versus single treadmill training (STT) on cognitive and walking performance under both single and dual task conditions, as well as on fall, patients’ subjective feeling, and quality of life. Sixteen individuals with PD were randomly assigned to DTT or STT group and underwent 8 weeks of training. The DTT group received treadmill training with cognitive loads, while the STT group received treadmill training without cognitive load. Outcome measures included gait parameters (speed, step length) and cognitive performance (reaction time, accuracy, composite score) under both single and dual task conditions. Unified Parkinson’s Disease Rating Scale-part III (UPDRS-III), Falls Efficacy Scale (FES), Patient Global Impression of Change (PGIC), and Parkinson’s Disease Questionnaire (PDQ-39) were also measured. Both DTT and STT groups showed increased comfortable walking speed and step length. Only the DTT group demonstrated significant improvements in cognitive composite score under both single and dual task conditions, as well as UPDRS-III, FES, and PDQ-39(p

Background & Purpose Falls and balance issues are significant concerns for the elderly. Treadmill training is increasingly recognized as a potential intervention to improve balance and reduce fall risk in this population. This systematic review evaluates the effectiveness of treadmill training on balance in the elderly. Methods A comprehensive search was conducted in databases including MEDLINE, EMBASE, CINAHL Plus, PEDro, Cochrane Library, and ERIC from January 1, 1980, to January 1, 2025. The search focused on treadmill training’s impact on balance in older adults. From 74 identified studies, primary outcome measure was “Balance Improvement, risk of fall” and secondary were “Cognitive Function and Quality of Life,” and others. Articles were excluded for reasons like irrelevance to treadmill training, language barriers, or duplication, resulting in 16 final studies. Results Treadmill training demonstrated positive effects on balance and fall risk reduction, particularly in elderly individuals with Parkinson’s disease, spinal cord injuries, and age-related balance issues. Perturbation-based treadmill training significantly reduced fall rates, while underwater treadmill sessions improved mobility and cognitive function. Conclusion Treadmill training interventions are promising for improving balance and mobility in the elderly, including those with Parkinson’s disease, spinal cord injuries, and age-related balance issues. While these interventions show potential, further research is needed to determine optimal protocols, durations, and combinations with other interventions. This could lead to a more comprehensive approach for addressing balance and mobility challenges in the elderly, promoting healthy aging and reducing fall risks.

Background Objective Methods Results Conclusions Reduced step length is a hallmark of gait disturbance in people with Parkinson's disease (PD). Although treadmill training is effective for improving step length, the associated neural mechanisms have not been fully investigated. Moreover, exploring the baseline neurophysiological predictors for step length improvement after training could facilitate personalized gait rehabilitation for PD.The aim of this study was to investigate the neuroplastic changes in corticomotor excitability after treadmill training and to explore whether baseline neurophysiological measures could predict step length improvement in PD.Data from 61 participants with idiopathic PD who completed 12 treadmill training sessions were included. Gait performances and corticomotor excitability measured by transcranial magnetic stimulation (TMS) were obtained at baseline, postintervention, and 1‐month follow‐up. TMS outcomes included motor‐evoked potentials, cortical silent period (CSP), intracortical facilitation (ICF), and short‐interval intracortical inhibition (SICI). General estimating equation analysis and principal‐component analyses were used to determine the neuroplastic changes induced by training, and multiple linear regression analysis was performed to explore the baseline TMS predictors for step length improvement at 1‐month follow‐up.After treadmill training, SICI and CSP significantly increased and shared an emerging relationship. Regression analysis showed that female sex and greater baseline ICF and SICI were significant predictors of step length improvement at the follow‐up.This study advanced the understanding of neuroplastic changes induced by treadmill training in PD and showed that preserved SICI and ICF were predictors for lasting step length improvement after training. Future studies could investigate other influential factors for treadmill training in PD. © 2024 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Metabolic flexibility describes the capability to switch between oxidative fuels depending on their availability during diet or exercise. In a previous study, we demonstrated that in response to training, marathon (DUhTP) mice, paternally selected for high treadmill performance, are metabolically more flexible than unselected control (DUC) mice. Since exercise-associated metabolic flexibility can be assessed by indirect calorimetry or partially by circulating lactate concentrations, we investigated these parameters in DUhTP and DUC mice. Therefore, males of both lines completed a three-week high-speed treadmill training or were physically inactive (sedentary) before being placed in a metabolic cage for three days (one day of acclimatization, two days with monitoring), measuring CO2 and O2 to calculate respiratory quotient (RQ) and fatty acid oxidation (FATox). Circulating blood lactate concentrations were determined. Training resulted in a lower RQ in DUhTP and an increased RQ in DUC mice compared to their sedentary counterparts. Increased FATox rates and lower lactate concentrations were observed in exercised DUhTP but not in DUC mice, indicating a shift to oxidative metabolism in DUhTP and a glycolytic one in DUC mice. Therefore, improved metabolic flexibility in DUhTP mice is verifiable up to three days after training. [ABSTRACT FROM AUTHOR]

Dual cognitive-walking treadmill training (DTT), designed to replicate real-life walking conditions, has shown promise effect in individuals with Parkinson's disease (PD). This study aims to compare the effects of DTT versus single treadmill training (STT) on cognitive and walking performance under both single and dual task conditions, as well as on fall, patients' subjective feeling, and quality of life. Sixteen individuals with PD were randomly assigned to DTT or STT group and underwent 8 weeks of training. The DTT group received treadmill training with cognitive loads, while the STT group received treadmill training without cognitive load. Outcome measures included gait parameters (speed, step length) and cognitive performance (reaction time, accuracy, composite score) under both single and dual task conditions. Unified Parkinson's Disease Rating Scale-part III (UPDRS-III), Falls Efficacy Scale (FES), Patient Global Impression of Change (PGIC), and Parkinson's Disease Questionnaire (PDQ-39) were also measured. Both DTT and STT groups showed increased comfortable walking speed and step length. Only the DTT group demonstrated significant improvements in cognitive composite score under both single and dual task conditions, as well as UPDRS-III, FES, and PDQ-39(p < 0.05). DTT can enhance cognitive function without compromising walking ability and also have real-world transferability. [ABSTRACT FROM AUTHOR]

Cable-driven robots are commonly applied in the rehabilitation field. Many tendon-based systems use parallel end-effector structures because of the advantages of fast reactions and high force outputs. We previously developed an active cable-driven robotic system that enabled accurate force control and was applied while walking on a treadmill. However, the kinematic and kinetic assistance methods need to be improved. Given the advantages of tendon-based parallel systems, this study investigated walking generated by four cables that were directly attached around the ankle. The aim of this work was to develop a tendon-based parallel robotic system to provide assisted walking on a treadmill with gait-specific position guidance and force compensation. To demonstrate the assistance effects, preliminary physiological responses of leg muscles during walking with the system were investigated. A parallel robotic system with four cable-driven units was developed. Kinematic and kinetic analyses of walking were performed, followed by the development of control algorithms for walking with impedance assistance only and walking with impedance assistance plus kinetic compensation. The muscle activity of the rectus femoris, vastus lateralis, gluteus maximus, biceps femoris, and gastrocnemius muscles was recorded and analyzed. On the basis of the kinematic and kinetic analyses, the tendon-based parallel robotic system produced treadmill walking with position and force assistance. The force control algorithms tracked the target force profile with a mean error of 6.4 N. During impedance-assisted walking, the rectus femoris, gluteus maximus and biceps femoris muscles produced a mean electromyography of 115.1% of the activity during independent walking (without assistance). However, the activity of the vastus lateralis and gastrocnemius reduced to only 82.5% of that during independent walking. Further kinetic compensation generally reduced the muscle activity, with the mean electromyography result being 88.7% of that during independent walking. From a technical point of view, the tendon-based parallel robotic system provided walking-specific position and force assistance in leg movement, accompanied by reduced muscle activity compared with independent walking. A technical feasibility study will be conducted to evaluate whether the tendon-based parallel robotic system is feasible for assisted treadmill walking in the general population and whether position guidance and force assistance are acceptable. [ABSTRACT FROM AUTHOR]

Objective: To observe the effects of Jiaji electroacupuncture combined with treadmill running training on tibial bone density, volume and number of blood vessels and VEGF expression after sciatic nerve amputation injury in rats, and provide theoretical basis for promoting tibial reconstruction after Jiaji electroacupuncture combined with treadmill running training. Method: A total of 180 SD rats were randomly divided into normal control group, model control group, Jiaji electroacupuncture group, treadmill group, combination treatment group (Jiaji electroacupuncture + treadmill), with 36 rats in each group. After 2, 4 and 8 weeks of postoperative intervention, the rats were divided into 3 subgroups, 12 in each subgroup. The model was made by suture of sciatic nerve dissociation injury. The normal control group received no intervention; the model control group received no intervention post-modeling. The Jiaji electroacupuncture group, treadmill group and combined group began to receive Jiaji electroacupunc ture, treadmill training and combined treatment respectively on the 3rd day after surgery. Bone density of tibia was analyzed by Micro-CT scan. The number and volume of the proximal tibial vessels were analyzed by angiography. The expression of VEGF mRNA and protein in tibia was detected by RT- PCR and Western Blot. VEGF concentration in tibial bone marrow was determined by ELISA. Result: At 2, 4 and 8 weeks post- intervention, the model control group showed significantly lower tibial bone mineral density, proximal vascular volume and quantity, VEGF mRNA and protein expression in bone tissue, and VEGF concentration in bone marrow compared to the normal control group at the same time point (P<0.05). However, overtime, the tibial bone mineral density, the volume and number of proximal blood vessels, VEGF mRNA and protein expression in bone tissue and VEGF concentration in bone marrow of rats in the Jiaji electroacupuncture group, treadmill group and combination group were significantly higher than those in the model control group at the same time point (P<0.05), and the combination group showed the most pronounced effects (P<0.05). Conclusion: Jiaji electroacupuncture combined with treadmill training may improve tibial bone mineral density by up-regulating the expression of VEGF in tibia and bone marrow. [ABSTRACT FROM AUTHOR]

Cerebral palsy (CP) is defined as a set of developmental illnesses that affect posture and mobility, causing activity restriction owing to abnormalities that are not progressive in the developing brain of the foetus or neonate. Children with cerebellar ataxic cerebral palsy often exhibit undeveloped or malformed cerebellar structures, resulting in challenges for the cerebellum to integrate the neural input required to control movement and balance smoothly. Patients with cerebellar ataxic cerebral palsy have difficulty in maintaining balance and trunk control which leads to difficulty in performing their activities of daily living and result in dependency. Thus, reporting cases like these is crucial to evaluate the impact of core stabilization intervention and treadmill walking on balance in a child having cerebellar ataxic cerebral palsy. A 7-year-old female child born at full term delivered via normal vaginal delivery with a birth weight of 2700 gm had no difficulties during antenatal, natal or postnatal phases. At the age of 6 years, mother noticed that the child had difficulty in standing and walking independently, she had difficulty in performing her activities of daily living independently. The patient underwent an 8 weeks intervention consisting of core stabilization exercise protocol and treadmill walking along with traditional physiotherapy intervention. The outcome measures included Paediatric Balance Scale for static balance and My Fitness Trainer (MFT)for dynamic balance. The patient showed significant improvement in both static as well as dynamic balance following the intervention. Thus, combined impact of core stabilization exercise protocol and treadmill walking can bring early effective changes on balance in a patient with cerebellar ataxic cerebral palsy. [ABSTRACT FROM AUTHOR]

IntroductionParkinson’s disease (PD) is characterized by progressive neurodegeneration within the nigrostriatum, leading to motor dysfunction. This systematic review aimed to summarize the effects of various exercise training regimens on protein or gene expression within the nigrostriatum and their role in neuroprotection and motor function improvement in animal models of Parkinson’s disease (PD).MethodsPubMed, EMBASE, and Web of Science were searched up to June 2024 and included sixteen studies that adhere to PRISMA guidelines and CAMARADES checklist scores ranging from 4 to 6 out of 10. Various exercise training regimens, administered 5 days per week for 6.5 weeks, were applied to MPTP, 6-OHDA, and PFF-α-synuclein-induced PD animal models.ResultsExercise training was found to downregulate the inflammatory pathway by attenuating α-synuclein aggregation, inhibiting the TLR/MyD88/IκBα signaling cascade and NF-κB phosphorylation, and decreasing pro-inflammatory cytokines IL-1β and TNF-α while increasing anti-inflammatory cytokines IL-10 and TGF-β within the nigrostriatum. It also inhibited the ASC and NLRP3 inflammasome complex and reduced the BAX/ Bcl-2 ratio and caspase-1/3 proteins, thereby decreasing neuronal apoptosis in the nigrostriatum. Exercise training elevated the expression of Pro-BDNF, BDNF, GDNF, TrkB, and Erk1/2, providing neurotrophic support to dopaminergic neurons. Furthermore, it upregulated the dopaminergic signaling pathway by increasing the expression of TH, DAT, PSD-95, and synaptophysin in the nigrostriatum.DiscussionThe findings suggested that exercise training downregulated inflammatory and apoptotic pathways while upregulated BDNF/GDNF pathways and dopaminergic signaling within the nigrostriatum. These molecular changes contributed to neuroprotection, reduced dopaminergic neuron loss, and improved motor function in PD animal models.Systematic review registrationCRD42024484537 https://www.crd.york.ac.uk/prospero/#recordDetails.

Juan Li,1,&ast; Ting Zhou,1,&ast; Pei Wang,1,&ast; Ruian Yin,1 Shengqi Zhang,1 Yile Cao,1 Lijuan Zong,1 Ming Xiao,2 Yongjie Zhang,3 Wentao Liu,4 Lingxiao Deng,5 Fei Huang,6 Jianfei Sun,7,&ast; Hongxing Wang1,&ast; 1Department of Rehabilitation Medicine, Zhongda Hospital Southeast University, Nanjing, 210024, People’s Republic of China; 2Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, 211166, People’s Republic of China; 3Department of Human Anatomy, Nanjing Medical University, Nanjing, 211166, People’s Republic of China; 4Department of Pharmacology, Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, 211166, People’s Republic of China; 5Department of Neurological Surgery, Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Indianapolis, IN, 46202-2266, USA; 6Institute of Neurobiology, Binzhou Medical University, Yantai, 264003, People’s Republic of China; 7State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory of Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210009, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianfei Sun, State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory of Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210009, People’s Republic of China, Email sunzaghi@seu.edu.cn Hongxing Wang, Department of Rehabilitation Medicine, Southeast University Zhongda Hospital, Nanjing, 210024, People’s Republic of China, Email 101012648@seu.edu.cnBackground: Gigantocellular reticular nucleus (GRNs) executes a vital role in locomotor recovery after spinal cord injury. However, due to its unique anatomical location deep within the brainstem, intervening in GRNs for spinal cord injury research is challenging. To address this problem, this study adopted an extracorporeal magnetic stimulation system to observe the effects of selective magnetic stimulation of GRNs with iron oxide nanoparticles combined treadmill training on locomotor recovery after spinal cord injury, and explored the possible mechanisms.Methods: Superparamagnetic iron oxide (SPIO) nanoparticles were stereotactically injected into bilateral GRNs of mice with moderate T10 spinal cord contusion. Eight-week selective magnetic stimulation produced by extracorporeal magnetic stimulation system (MSS) combined with treadmill training was adopted for the animals from one week after surgery. Locomotor function of mice was evaluated by the Basso Mouse Scale, Grid-walking test and Treadscan analysis. Brain MRI, anterograde virus tracer and immunofluorescence staining were applied to observe the tissue compatibility of SPIO in GRNs, trace GRNs’ projections and evaluate neurotransmitters’ expression in spinal cord respectively. Motor-evoked potentials and H reflex were collected for assessing the integrity of cortical spinal tract and the excitation of motor neurons in anterior horn.Results: (1) SPIO persisted in GRNs for a minimum of 24 weeks without inducing apoptosis of GRN cells, and degraded slowly over time. (2) MSS-enabled treadmill training dramatically improved locomotor performances of injured mice, and promoted cortico-reticulo-spinal circuit reorganization. (3) MSS-enabled treadmill training took superimposed roles through both activating GRNs to drive more projections of GRNs across lesion site and rebalancing neurotransmitters’ expression in anterior horn of lumbar spinal cord.Conclusion: These results indicate that selective MSS intervention of GRNs potentially serves as an innovative strategy to promote more spared fibers of GRNs across lesion site and rebalance neurotransmitters’ expression after spinal cord injury, paving the way for the structural remodeling of neural systems collaborating with exercise training, thus ultimately contributing to the reconstruction of cortico-reticulo-spinal circuit. Keywords: gigantocellular reticular nucleus, locomotion, magnetic stimulation, spinal cord injury, superparamagnetic iron oxide nanoparticles, treadmill training

Structural neuroplasticity such as neurite extension and dendritic spine dynamics is enhanced by brain-derived neurotrophic factor (BDNF) and impaired by types of inhibitory molecules that induce growth cone collapse and actin depolymerization, for example, myelin-associated inhibitors, chondroitin sulfate proteoglycans, and negative guidance molecules. These inhibitory molecules can activate RhoA/rho-associated coiled-coil containing protein kinase (ROCK) signaling (known to restrict structural plasticity). Intermittent hypoxia (IH) and high-intensity interval training (HIIT) are known to upregulate BDNF that is associated with improvements in learning and memory and greater functional recovery following neural insults. We investigated whether the RhoA/ROCK signaling pathway is also modulated by IH and HIIT in the hippocampus, cortex, and lumbar spinal cord of male Wistar rats. The gene expression of 25 RhoA/ROCK signaling pathway components was determined following IH, HIIT, or IH combined with HIIT (30 min/day, 5 days/wk, 6 wk). IH included 10 3-min bouts that alternated between hypoxia (15% O2) and normoxia. HIIT included 10 3-min bouts alternating between treadmill speeds of 50 cm·s−1 and 15 cm·s−1. In the hippocampus, IH and HIIT significantly downregulated Acan and NgR2 mRNA that are involved in the inhibition of neuroplasticity. However, IH and IH + HIIT significantly upregulated Lingo-1 and NgR3 in the cortex. This is the first time IH and HIIT have been linked to the modulation of plasticity-inhibiting pathways. These results provide a fundamental step toward elucidating the interplay between the neurotrophic and inhibitory mechanisms involved in experience-driven neural plasticity that will aid in optimizing physiological interventions for the treatment of cognitive decline or neurorehabilitation. NEW & NOTEWORTHY: Intermittent hypoxia (IH) and high-intensity interval training (HIIT) enhance neuroplasticity and upregulate neurotrophic factors in the central nervous system (CNS). We provide evidence that IH and IH + HIIT also have the capacity to regulate genes involved in the RhoA/ROCK signaling pathway that is known to restrict structural plasticity in the CNS. This provides a new mechanistic insight into how these interventions may enhance hippocampal-related plasticity and facilitate learning, memory, and neuroregeneration. [ABSTRACT FROM AUTHOR]

Objective To determine the effects of treadmill training on the structure of hippocampal myelin and cognitive function in rats exposed to acute plateau hypoxia. Methods With 30 SPF-grade female SD rats (aged 6-8 weeks, weighing 200-220 g), 6 of them were used for observation of myelin structure after injury, and the remaining 24 rats were randomly divided into control group, hypobaric hypoxia group and treadmill training group (n=8). The rats in above experimental groups were placed in a low-pressure oxygen chamber at an altitude of 6 000 m for 7 consecutive days, and the rats of the control group were placed in the confined chamber for the same period without hypoxia. Then, the rats of the treadmill training group received a 4-week treadmill training scheme since the day after hypoxia. Finally, all the rats were tested for cognitive function with open field test (OFT) and Morris water maze (MWM). Transmission electron microscopy (TEM) was used to observe the changes of demyelination in the hippocampus. The expression of oligodendrocyte transcription factor 2 (Olig2) and myelin basic protein (MBP) in the hippocampal CA1 and CA3 regions was measured by immunofluorescence staining and Western blotting. Results Behavioral tests showed that the number into the central area, total distance, distance ratio in OFT and the number of platform crossings and distance to the target area in MWM were reduced in the hypobaric hypoxia group than the control group (P < 0.05), while these indexes were increased in the treadmill training group than in the hypobaric hypoxia group (P < 0.05). Immunofluorescence staining indicated that the number of Olig2 positive cells per unit area and the mean fluorescence intensity of MBP in the CA1 and CA3 regions were significantly lessen in the hypobaric hypoxia group than the control group (P < 0.05), while these indicators were higher in the treadmill training group than the hypobaric hypoxia group (P < 0.05). Western blotting displayed that the expression levels of Olig2 and MBP in the hippocampus were obviously lower in the hypobaric hypoxia group than the control group (P < 0.01), while the levels were increased in the treadmill training group than the hypobaric hypoxia group (P < 0.01). Conclusion Treadmill training promotes the number of the oligodendrocyte spectrum cells in CA1 and CA3 regions, enhances the expression of myelin-related proteins and improves myelin repair in hippocampus of hypobaric hypoxia rats, and thereby ameliorates hypoxia-induced anxiety-like behaviors and memory dysfunction.

Abstract Secondary lung injury after SCI is a major cause of patient mortality, with apoptosis playing a key role. This study aimed to explore the impact of treadmill training and miR145-5p on the MAPK/Erk signaling pathway and apoptosis in rats with complete SCI. SD rats were used to establish T10 segmental complete SCI models and underwent treadmill training 3, 7, or 14 days postinjury. Various techniques including arterial blood gas analysis, lung wet/dry weight ratio, HE staining, immunofluorescence staining, immunohistochemical staining, qRT-PCR, and Western blotting were employed to assess alterations in lung function and the expression levels of crucial apoptosis-related factors. In order to elucidate the specific mechanism, the impact of miR145-5p on the MAPK/Erk pathway and its role in apoptosis in lung cells were confirmed through miR145-5p overexpression and knockdown experiments. Following spinal cord injury (SCI), an increase in apoptosis, activation of the MAPK/Erk pathway, and impairment of lung function were observed in SCI rats. Conversely, treadmill training resulted in a reduction in alveolar cell apoptosis, suppression of the MAPK/Erk pathway, and enhancement of lung function. The gene MAP3K3 was identified as a target of miR145-5p. The influence of miR145-5p on the MAPK/Erk pathway and its impact on apoptosis in alveolar cells were confirmed through the manipulation of miR145-5p expression levels. The upregulation of miR145-5p in spinal cord injury (SCI) rats led to a reduction in MAP3K3 protein expression within lung tissues, thereby inhibiting the MAPK/Erk signaling pathway and decreasing apoptosis. Contrarily, rats with miR145-5p knockdown undergoing treadmill training exhibited an increase in miR145-5p expression levels, resulting in the inhibition of MAP3K3 protein expression in lung tissues, suppression of the MAPK/Erk pathway, and mitigation of lung cell apoptosis. Ultimately, the findings suggest that treadmill training may attenuate apoptosis in lung cells post-spinal cord injury by modulating the MAP3K3 protein through miR145-5p to regulate the MAPK/Erk signaling pathway.

Secondary lung injury after SCI is a major cause of patient mortality, with apoptosis playing a key role. This study aimed to explore the impact of treadmill training and miR145-5p on the MAPK/Erk signaling pathway and apoptosis in rats with complete SCI. SD rats were used to establish T10 segmental complete SCI models and underwent treadmill training 3, 7, or 14 days postinjury. Various techniques including arterial blood gas analysis, lung wet/dry weight ratio, HE staining, immunofluorescence staining, immunohistochemical staining, qRT-PCR, and Western blotting were employed to assess alterations in lung function and the expression levels of crucial apoptosis-related factors. In order to elucidate the specific mechanism, the impact of miR145-5p on the MAPK/Erk pathway and its role in apoptosis in lung cells were confirmed through miR145-5p overexpression and knockdown experiments. Following spinal cord injury (SCI), an increase in apoptosis, activation of the MAPK/Erk pathway, and impairment of lung function were observed in SCI rats. Conversely, treadmill training resulted in a reduction in alveolar cell apoptosis, suppression of the MAPK/Erk pathway, and enhancement of lung function. The gene MAP3K3 was identified as a target of miR145-5p. The influence of miR145-5p on the MAPK/Erk pathway and its impact on apoptosis in alveolar cells were confirmed through the manipulation of miR145-5p expression levels. The upregulation of miR145-5p in spinal cord injury (SCI) rats led to a reduction in MAP3K3 protein expression within lung tissues, thereby inhibiting the MAPK/Erk signaling pathway and decreasing apoptosis. Contrarily, rats with miR145-5p knockdown undergoing treadmill training exhibited an increase in miR145-5p expression levels, resulting in the inhibition of MAP3K3 protein expression in lung tissues, suppression of the MAPK/Erk pathway, and mitigation of lung cell apoptosis. Ultimately, the findings suggest that treadmill training may attenuate apoptosis in lung cells post-spinal cord injury by modulating the MAP3K3 protein through miR145-5p to regulate the MAPK/Erk signaling pathway. [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) presents a complex challenge in neurorehabilitation, demanding innovative therapeutic strategies to facilitate functional recovery. This study investigates the effects of treadmill training on SCI recovery, emphasizing motor function enhancement, neural tissue preservation, and axonal growth. Our research, conducted on a rat model, demonstrates that controlled treadmill exercises significantly improve motor functions post-SCI, as evidenced by improved scores on the Basso, Beattie, and Bresnahan (BBB) locomotor rating scale and enhanced electromyography readings. Notably, the training facilitates the preservation of spinal cord tissue, effectively reducing secondary damage and promoting the maintenance of neural fibers in the injured area. A key finding is the significant stimulation of axonal growth around the injury epicenter in trained rats, marked by increased growth-associated protein 43 (GAP43) expression. Despite these advancements, the study notes a limited impact of treadmill training on motoneuron adaptation and highlights minimal changes in the astrocyte and neuron–glial antigen 2 (NG2) response. This suggests that, while treadmill training is instrumental in functional improvements post-SCI, its influence on certain neural cell types and glial populations is constrained. [ABSTRACT FROM AUTHOR]

Stroke rehabilitation interventions require multiple training sessions and repeated assessments to evaluate the improvements from training. Biofeedback-based treadmill training often involves 10 or more sessions to determine its effectiveness. The training and assessment process incurs time, labor, and cost to determine whether the training produces positive outcomes. Predicting the effectiveness of gait training based on baseline minimum foot clearance (MFC) data would be highly beneficial, potentially saving resources, costs, and patient time. This work proposes novel features using the Short-term Fourier Transform (STFT)-based magnitude spectrum of MFC data to predict the effectiveness of biofeedback training. This approach enables tracking non-stationary dynamics and capturing stride-to-stride MFC value fluctuations, providing a compact representation for efficient processing compared to time-domain analysis alone. The proposed STFT-based features outperform existing wavelet, histogram, and Poincaré-based features with a maximum accuracy of 95%, F1 score of 96%, sensitivity of 93.33% and specificity of 100%. The proposed features are also statistically significant (p

Abstract Background and aim Post-traumatic osteoarthritis (PTOA) is a subtype of osteoarthritis (OA). Exercise may produce and release the myokine irisin through muscle fiber contraction. However, the effect of exercise-promoted irisin production on the internal interactions of the muscle–bone unit in PTOA studies remains unclear. Methods Eighteen 8-week-old Sprague–Dawley (SD) rats were randomly divided into three groups: Sham/sedentary (Sham/Sed), PTOA/sedentary (PTOA/Sed), and PTOA/treadmill-walking (PTOA/TW). The PTOA model was established by transection of anterior cruciate ligament (ACLT) and destabilization of medial meniscus (DMM). After 4 weeks of modeling, the PTOA/TW group underwent treadmill exercise (15 m/min, 30 min/d, 5 d/ week, 8 weeks), and the other two groups were free to move in the cage. Evaluation and correlation analysis of muscle, cartilage, subchondral bone and serological indexes were performed after euthanasia. Results Eight weeks of treadmill exercise effectively alleviated the trauma-induced OA phenotype, thereby maintaining cartilage and subchondral bone integrity in PTOA, and reducing quadriceps atrophy and myofibril degradation. Exercise reversed the down-regulated expression of peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) and fibronectin type III structural domain protein 5 (FNDC5) in muscle tissue of PTOA rats, and increased the blood irisin level, and the irisin level was positively correlated with the expression of PGC-1α and FNDC5. In addition, correlation analysis showed that irisin metabolism level was strongly negatively correlated with Osteoarthritis Research Society International (OARSI) and subchondral bone loss, indicating that irisin may be involved in cartilage biology and PTOA-related changes in cartilage and subchondral bone. Moreover, the metabolic level of irisin was strongly negatively correlated with muscle fiber cross-sectional area (CSA), Atrogin-1 and muscle ring-finger protein-1(MuRF-1) expression, suggesting that irisin may alleviate muscle atrophy through autocrine action. Conclusion Treadmill exercise can alleviate the atrophy and degeneration of muscle fibers in PTOA rats, reduce the degradation of muscle fibrin, promote the expression of serum irisin, and alleviate the degeneration of articular cartilage and subchondral bone loss in PTOA rats. These results indicate that treadmill exercise can affect the process of PTOA by promoting the expression of myokine irisin in rat muscle–bone unit.

Background & Purpose Falls and balance issues are significant concerns for the elderly. Treadmill training is increasingly recognized as a potential intervention to improve balance and reduce fall risk in this population. This systematic review evaluates the effectiveness of treadmill training on balance in the elderly. Methods A comprehensive search was conducted in databases including MEDLINE, EMBASE, CINAHL Plus, PEDro, Cochrane Library, and ERIC from January 1, 1980, to May 31, 2023. The search focused on treadmill training’s impact on balance in older adults. From 74 identified studies, outcome measures were categorized into groups like “Balance Improvement,” “Gait Improvement,” “Mobility Enhancement,” “Muscle Strength Improvement,” “Cognitive Function and Quality of Life,” and others. Articles were excluded for reasons like irrelevance to treadmill training, language barriers, or duplication, resulting in 16 final studies. Results Treadmill training shows diverse positive effects on the elderly. Perturbation-based training reduces falls, and treadmill walking enhances balance and quality of life, particularly in institutionalized older individuals. Benefits were noted for Parkinson’s patients’ gait, cognitive changes in neurophysiology, fitness and mobility improvements through underwater treadmill sessions, and refined gait in hemiparetic patients. Conclusion Treadmill training interventions are promising for improving balance and mobility in the elderly, including those with Parkinson’s disease, spinal cord injuries, and age-related balance issues. While these interventions show potential, further research is needed to determine optimal protocols, durations, and combinations with other interventions. This could lead to a more comprehensive approach for addressing balance and mobility challenges in the elderly, promoting healthy aging and reducing fall risks.

Abstract In this study, we examined the combined impact of osteopontin (OPN) and treadmill training on mice with spinal cord injury (SCI). OPN was overexpressed by injecting AAV9-SPP1-GFP into the sensorimotor cortex, followed by a left incomplete C5 crush injury two weeks later. Mice (Ex or Ex + OPN group) were trained at 50% maximum running speed for 8 weeks. To analyze the effects, we used biotinylated dextran amine (BDA) for tracing the corticospinal tract (CST) and performed Western blotting and immunohistochemical methods to assess the activation of the mammalian target of rapamycin (mTOR). We also examined axonal regeneration and conducted behavioral tests to measure functional recovery. The results demonstrated that treadmill training promoted the expression of neurotrophic factors such as brain-derived neurotrophic factor (BNDF) and insulin-like growth factor I (IGF-1) and activated mTOR signaling. OPN amplified the effect of treadmill training on activating mTOR signaling indicated by upregulated phosphorylation of ribosomal protein S6 kinase (S6). The combination of OPN and exercise further promoted functional recovery and facilitated limited CST axonal regeneration which did not occur with treadmill training and OPN treatment alone. These findings indicate that OPN enhances the effects of treadmill training in the treatment of SCI and offer new therapeutic insights for spinal cord injury.

الملخص: أهداف البحث: يستهلك المشي الرجعي أو المشي للخلف طاقة أكبر ويضع ضغطا أقل على المفاصل مقارنة بالمشي إلى الأمام بسرعة مماثلة. هدفت هذه الدراسة التي أجريت على الشباب البدينين في المقام الأول إلى مقارنة تأثيرات المشي إلى الوراء مع تأثيرات المشي إلى الأمام على مستويات الأديبونكتين. كان الهدف الثانوي هو وصف تأثيرات العوامل المصاحبة وهي البروتين المتفاعل-سي، ومؤشر كتلة الجسم، ونسبة الخصر إلى الطول ونسبة الخصر إلى الورك على مستويات الأديبونيكتين لدى الشباب البدينين. طريقة البحث: في هذه الدراسة التجريبية العشوائية المقارنة، خضع مائة واثنان من المشاركين إما للتدريب على المشي الرجعي أو المشي للأمام أربع مرات في الأسبوع لمدة اثني عشر أسبوعا قبل وبعد ذلك أديبونيكتين، البروتين المتفاعل-سي، مؤشر كتلة الجسم، نسبة الخصر إلى الطول، ونسبة الخصر إلى الورك تم قياسها. تم إجراء مقارنة بين القيم المقاسة قبل وبعد التدخل وبين المجموعات وتم تحديد تأثير البروتين المتفاعل-سي ومؤشر كتلة الجسم ونسبة الخصر إلى الطول ونسبة الخصر إلى الورك على مستويات الأديبونكتين. النتائج: زادت مستويات أديبونيكتين بشكل ملحوظ وانخفض البروتين المتفاعل-سي ومؤشر كتلة الجسم ونسبة الخصر إلى الطول ونسبة الخصر إلى الورك بشكل ملحوظ بعد التدخل. أظهر المشاركون الذين خضعوا لتدريب المشي الرجعي تغيرا أعلى بشكل ملحوظ في مستويات البروتين المتفاعل-سي، ومؤشر كتلة الجسم ونسبة الخصر إلى الورك مقارنة بمجموعة المشي إلى الأمام. شوهدت مستويات أديبونيكتين تتأثر بمؤشر كتلة الجسم الاستنتاجات: يؤدي تدريب المشي الرجعي إلى زيادة أكبر في الأديبونيكتين وتقليل البروتين المتفاعل-سي، ومؤشر كتلة الجسم، ونسبة الخصر إلى الطول ونسبة الخصر إلى الورك مقارنة بالمشي إلى الأمام، وتتأثر مستويات الأديبونكتين بمؤشر كتلة الجسم. يمكن استخدام التدريب على جهاز المشي الرجعي بشكل تفضيلي لتقليل عوامل الخطر القلبية الوعائي. Abstract: Objectives: Retro walking or backward walking expends greater energy and places less stress on joints compared with forward walking at a similar speed. This study conducted in obese young men was primarily aimed at comparing the effects of backward walking with forward walking on adiponectin levels. The secondary aim was to describe the effects of concomitant factors, namely C-reactive protein, body mass index (BMI), waist to height ratio, and waist to hip ratio, on adiponectin levels in obese young men. Methods: In this randomized comparative study, 102 participants underwent either retro walking or forward walking treadmill training four times a week for 12 weeks before and after which adiponectin, C-reactive protein, BMI, waist to height ratio, and waist to hip ratio were measured. Comparison of the measured values before and after intervention and between the groups was done, and the influence of C-reactive protein, BMI, waist to height ratio, and waist to hip ratio on adiponectin levels was determined. Results: Adiponectin levels were significantly increased (p

• Baseline patient characteristics could predict the benefits of treadmill training • Biological sex predicts the improvement in motor function • Baseline balance confidence and velocity are key predictors for improved gait speed • Increased quality of life is predicted by a poorer baseline value • Cut-off points are provided to target suitable candidates for treadmill training To explore the potential predictors of people with Parkinson disease (PD) who would benefit the most from treadmill training. A cohort study. Medical university rehabilitation settings. Seventy participants diagnosed of idiopathic PD. Twelve sessions of treadmill training. Hierarchical logistic regression models were used to explore significant predictors of the treadmill training effect with respect to 3 health domains: Unified Parkinson's Disease Rating Scales part III (UPDRS III); gait speed; Parkinson's Disease Questionnaire-39 (PDQ-39). A receiver operating characteristic (ROC) curve analysis was conducted to identify proper cut-off points for clinical use. Male sex (adjusted odds ratio [OR]: 3.73, P=.036) significantly predicted the improvement of UPDRS III. Individuals with a slower baseline gait speed (cut-off: 0.92 m/s, adjusted OR: 14.06, P<.001) and higher baseline balance confidence measured by the Activity-specific Balance Confidence scale (cut-off: 84.5 points, adjusted OR: 4.66, P=.022) have greater potential to achieve clinically relevant improvements in gait speed. A poorer baseline PDQ-39 score (cut-off: 23.1, adjusted OR: 7.47, P<.001) predicted a greater quality of life improvement after treadmill training. These findings provide a guideline for clinicians to easily identify suitable candidates for treadmill training. Generalization to more advanced patients with PD warrants further investigation. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the effects of aerobic treadmill training regimen of four weeks duration on oxidative stress parameters, metabolic enzymes, and histomorphometric changes in the colon of hyperhomocysteinemic rats. Male Wistar albino rats were divided into four groups (n = 10, per group): C, 0.9% NaCl 0.2 mL/day subcutaneous injection (s.c.) 2x/day; H, homocysteine 0.45 µmol/g b.w./day s.c. 2x/day; CPA, saline (0.9% NaCl 0.2 mL/day s.c. 2x/day) and an aerobic treadmill training program; and HPA, homocysteine (0.45 µmol/g b.w./day s.c. 2x/day) and an aerobic treadmill training program. The HPA group had an increased level of malondialdehyde (5.568 ± 0.872 μmol/mg protein, p = 0.0128 vs. CPA (3.080 ± 0.887 μmol/mg protein)), catalase activity (3.195 ± 0.533 U/mg protein, p < 0.0001 vs. C (1.467 ± 0.501 U/mg protein), p = 0.0012 vs. H (1.955 ± 0.293 U/mg protein), and p = 0.0003 vs. CPA (1.789 ± 0.256 U/mg protein)), and total superoxide dismutase activity (9.857 ± 1.566 U/mg protein, p < 0.0001 vs. C (6.738 ± 0.339 U/mg protein), p < 0.0001 vs. H (6.015 ± 0.424 U/mg protein), and p < 0.0001 vs. CPA (5.172 ± 0.284 U/mg protein)) were detected in the rat colon. In the HPA group, higher activities of lactate dehydrogenase (2.675 ± 1.364 mU/mg protein) were detected in comparison to the CPA group (1.198 ± 0.217 mU/mg protein, p = 0.0234) and higher activities of malate dehydrogenase (9.962 (5.752–10.220) mU/mg protein) were detected in comparison to the CPA group (4.727 (4.562–5.299) mU/mg protein, p = 0.0385). Subchronic treadmill training in the rats with hyperhomocysteinemia triggers the colon tissue antioxidant response (by increasing the activities of superoxide dismutase and catalase) and elicits an increase in metabolic enzyme activities (lactate dehydrogenase and malate dehydrogenase). This study offers a comprehensive assessment of the effects of aerobic exercise on colonic tissues in a rat model of hyperhomocysteinemia, evaluating a range of biological indicators including antioxidant enzyme activity, metabolic enzyme activity, and morphometric parameters, which suggested that exercise may confer protective effects at both the physiological and morphological levels. [ABSTRACT FROM AUTHOR]

Considering the alterations in gait patterns and increase in metabolic demands during walking on an inclined surface, inclined treadmill training (ITT) may be an alternative treatment to non-inclined treadmill training (NITT) for improving gait and balance among people with chronic stroke. We searched eight electronic databases (August 2021), assessed risk of bias (Cochrane RoB 2.0 tool), and meta-analysed data (RevMan 3.5). Results were reported according to the PRISMA guidelines. Outcomes were gait parameters such as walking speed and balance-related outcome measures such as Berg Balance Scale scores. Risk of bias assessment was performed according to Version 2 of the Cochrane risk-of-bias tool for randomised trials (RoB 2). Of the screened citations, four met our inclusion criteria. Quantitative analysis showed ITT was significant in improving walking speed, stride length, paretic step length, Berg Balance Scale scores and Overall Stability Index (p < 0.05) but not in cadence, non-paretic step length, stance time on the non-paretic and paretic leg (p > 0.05). Only one study was rated low risk of bias. There was limited evidence for the superiority of ITT over NITT, in adjunct to other conventional intervention, for improving gait and balance among chronic stroke patients. [ABSTRACT FROM AUTHOR]

Introduction: The healing of tendon-bone injuries is very difficult, often resulting in poor biomechanical performance and unsatisfactory functional recovery. The tendon-bone insertion has a complex four distinct layers structure, and previous studies have often focused on promoting the regeneration of the fibrocartilage layer, neglecting the role of its bone end repair in tendon-bone healing. This study focuses on the role of treadmill training in promoting bone regeneration at the tendon-bone insertion and its related mechanisms. Methods: After establishing the tendon-bone insertion injury model, the effect of treadmill training on tendon-bone healing was verified by Micro CT and HE staining; then the effect of CX3CL1 on osteoclast differentiation was verified by TRAP staining and cell culture; and finally the functional recovery of the mice was verified by biomechanical testing and behavioral test. Results: Treadmill training suppresses the secretion of CX3CL1 and inhibits the differentiation of local osteoclasts after tendon-bone injury, ultimately reducing osteolysis and promoting tendon bone healing. Discussion: Our research has found the interaction between treadmill training and the CX3CL1-C3CR1 axis, providing a certain theoretical basis for rehabilitation training. [ABSTRACT FROM AUTHOR]

Background and aim: Post-traumatic osteoarthritis (PTOA) is a subtype of osteoarthritis (OA). Exercise may produce and release the myokine irisin through muscle fiber contraction. However, the effect of exercise-promoted irisin production on the internal interactions of the muscle–bone unit in PTOA studies remains unclear. Methods: Eighteen 8-week-old Sprague–Dawley (SD) rats were randomly divided into three groups: Sham/sedentary (Sham/Sed), PTOA/sedentary (PTOA/Sed), and PTOA/treadmill-walking (PTOA/TW). The PTOA model was established by transection of anterior cruciate ligament (ACLT) and destabilization of medial meniscus (DMM). After 4 weeks of modeling, the PTOA/TW group underwent treadmill exercise (15 m/min, 30 min/d, 5 d/ week, 8 weeks), and the other two groups were free to move in the cage. Evaluation and correlation analysis of muscle, cartilage, subchondral bone and serological indexes were performed after euthanasia. Results: Eight weeks of treadmill exercise effectively alleviated the trauma-induced OA phenotype, thereby maintaining cartilage and subchondral bone integrity in PTOA, and reducing quadriceps atrophy and myofibril degradation. Exercise reversed the down-regulated expression of peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) and fibronectin type III structural domain protein 5 (FNDC5) in muscle tissue of PTOA rats, and increased the blood irisin level, and the irisin level was positively correlated with the expression of PGC-1α and FNDC5. In addition, correlation analysis showed that irisin metabolism level was strongly negatively correlated with Osteoarthritis Research Society International (OARSI) and subchondral bone loss, indicating that irisin may be involved in cartilage biology and PTOA-related changes in cartilage and subchondral bone. Moreover, the metabolic level of irisin was strongly negatively correlated with muscle fiber cross-sectional area (CSA), Atrogin-1 and muscle ring-finger protein-1(MuRF-1) expression, suggesting that irisin may alleviate muscle atrophy through autocrine action. Conclusion: Treadmill exercise can alleviate the atrophy and degeneration of muscle fibers in PTOA rats, reduce the degradation of muscle fibrin, promote the expression of serum irisin, and alleviate the degeneration of articular cartilage and subchondral bone loss in PTOA rats. These results indicate that treadmill exercise can affect the process of PTOA by promoting the expression of myokine irisin in rat muscle–bone unit. [ABSTRACT FROM AUTHOR]

Background: Stroke is the second most common cause of death due to disability in first world countries. Globally stroke is the main threshold of disability and functional loss, loss of function often leads to decrease walking endurance. Objective: The objective of the study is to determine the effectiveness of treadmill training with body weight support and strengthening exercises of lower limb on walking endurance among stroke patients. Methodology: The study design was a Randomized Control Trial.30 participants were selected, divided in to two groups, 15 in treadmill training with BWS and 15 in strengthening exercises of lower limb group. Outcome measure was walking endurance measured by 6 min walk test. Data was analyzed using SPSS (Statistical Package for Social Sciences.) version 21. Results: The mean pre and post scores of walking endurance was 189.66 ± 24.38 and 383.00 ± 85.39 in treadmill training with BWS group and 206.66 ± 31.94 and 301.33 ± 51.80 in lower limb strengthening exercises group. Both had p value <0.000. When mean comparison of walking endurance was done between both the group strengthening group showed 94.66 ± 32.86 score with p value <0.00 while in treadmill training with BWS group it jumped to 193.33 ± 79.13 with p value <0.000. Conclusion: Treadmill training with body weight support is more effective for walking endurance among stroke patients and it can be a choice of treatment for improvement of walking endurance in stroke patients. [ABSTRACT FROM AUTHOR]

BACKGROUND: Treadmill training is one of the effective ways to promote the recovery of motor function after spinal cord injury. Treadmill training can promote neurogenesis, but the effect of different intensities of treadmill training on the activation of endogenous stem cells is still unclear. OBJECTIVE: To analyze the activation effect of different intensities of treadmill training on endogenous neural stem cells in the spinal cord of mice after spinal cord injury. METHODS: Fifty female C57BL/6J mice were divided into control group, spinal cord injury group, low-, moderate-, and high-intensity exercise groups with 10 mice in each group by random number table method. T10 segment spinal cord injury model was constructed by the clamp method in spinal cord injury group, low-, moderate-, and high-intensity exercise groups. On day 7 after spinal cord injury, mice in the low-, moderate-, and high-intensity exercise groups were respectively trained on the treadmill with corresponding intensity, 3 times /d, 10 min/ times, 6 times a week for 28 consecutive days. At 3, 7, 14, 21, and 28 days after treadmill training, the hind limb motor function was evaluated by BMS score. At 28 days after treadmill training, the spinal cord tissue of the injured area was obtained, and the expression of epidermal growth factor receptor, glial fibrillary acidic protein, and 5-Ethynyl-2'-deoxyuridine (EdU), a proliferative marker, was detected. Hematoxylin-eosin staining was used to observe the morphology of spinal cord. RESULTS AND CONCLUSION: (1) The BMS score of mice in the spinal cord injury group was lower than that in the control group (P < 0.05). With the extension of treadmill training time, the BMS scores of mice with spinal cord injury gradually increased, and the BMS scores of mice in moderate-intensity exercise group on days 14 and 21 after treadmill training were higher than those in spinal cord injury group and low- and high-intensity exercise groups (P < 0.05). The BMS score of mice in moderate- and high-intensity exercise group was higher than that in spinal cord injury group and low-intensity exercise group at 28 days after treadmill training (P < 0.05). (2) Compared with the control group, the proportion of epidermal growth factor receptor and EdU positive cells was increased in spinal cord injury group (P < 0.05). Compared with spinal cord injury group, the proportion of epidermal growth factor receptor and EdU positive cells was increased in low-, moderate-, and high-intensity exercise groups (P < 0.05), and the highest was found in moderate-intensity exercise group. Compared with control group, the proportion of glial fibrillary acidic protein positive cells was increased in spinal cord injury group (P < 0.05). Compared with spinal cord injury group, the proportion of glial fibrillary acidic protein positive cells was lower in low-, moderate-, and high-intensity exercise groups (P < 0.05), and the moderate-intensity exercise group was the lowest. (3) Hematoxylin-eosin staining showed that a large cavity was formed in the injured area of mice with spinal cord injury, and the cavity in the injured area of mice with spinal cord injury decreased after different intensities of treadmill training, and the decrease was most obvious in the moderate-intensity exercise group. (4) These results indicate that low-, moderate-, and high-intensity treadmill training can promote the recovery of motor function of mice with spinal cord injury by activating endogenous neural stem cells, and the effect of moderate-intensity exercise training is the most obvious. [ABSTRACT FROM AUTHOR]

Intervention parameters such as the challenge, amount, and dosage (challenge × amount) have the potential to alter the efficacy of rehabilitation interventions after stroke. This systematic review investigated the effect of intervention parameters of challenge, amount, and dosage on improvements in walking outcomes following treadmill training (TT) and comparison interventions in people with stroke. Randomized controlled trials were included if they: (i) investigated interventions of TT or bodyweight-supported TT (BWSTT); (ii) made comparisons with other physiotherapy interventions, other types of TT, or no intervention; (iii) studied people with stroke; (iv) reported sufficient data on challenge and amount parameters; and (v) measured walking speed or endurance. Completeness of reporting was evaluated using the TIDieR-Rehab checklist and risk of bias was assessed using the revised Cochrane risk-of-bias tool. The review included 26 studies; 15 studies compared TT or BWSTT with other physiotherapy interventions and 11 studies compared different types of TT. Meta-analyses provided evidence with low to moderate certainty that greater differences in challenge and dosage between treadmill and comparison physiotherapy interventions produced greater effects on walking endurance (p < 0.01). However, challenge and dosage did not influence walking speed outcomes. The analysis of intervention amount was limited by the lack of studies that manipulated the amount of intervention. Overall, the findings indicate that, after stroke, some of the efficacy of TT on walking endurance can be explained by the challenge level during training. This supports the implementation of TT at higher challenge levels in stroke rehabilitation practice. [ABSTRACT FROM AUTHOR]

In this study, we examined the combined impact of osteopontin (OPN) and treadmill training on mice with spinal cord injury (SCI). OPN was overexpressed by injecting AAV9-SPP1-GFP into the sensorimotor cortex, followed by a left incomplete C5 crush injury two weeks later. Mice (Ex or Ex + OPN group) were trained at 50% maximum running speed for 8 weeks. To analyze the effects, we used biotinylated dextran amine (BDA) for tracing the corticospinal tract (CST) and performed Western blotting and immunohistochemical methods to assess the activation of the mammalian target of rapamycin (mTOR). We also examined axonal regeneration and conducted behavioral tests to measure functional recovery. The results demonstrated that treadmill training promoted the expression of neurotrophic factors such as brain-derived neurotrophic factor (BNDF) and insulin-like growth factor I (IGF-1) and activated mTOR signaling. OPN amplified the effect of treadmill training on activating mTOR signaling indicated by upregulated phosphorylation of ribosomal protein S6 kinase (S6). The combination of OPN and exercise further promoted functional recovery and facilitated limited CST axonal regeneration which did not occur with treadmill training and OPN treatment alone. These findings indicate that OPN enhances the effects of treadmill training in the treatment of SCI and offer new therapeutic insights for spinal cord injury. [ABSTRACT FROM AUTHOR]

Background: Heterotopic ossification of tendons and ligaments (HOTL) is a common clinical condition characterized by the absence of discernible features and a lack of effective treatment. In vitro experiments have demonstrated that mechanical stimulation can induce cell differentiation toward osteogenesis, thereby promoting heterotopic ossification. Currently, there are few experimental designs aimed at inducing ligament stretching in mice, and the mechanism of heterotopic ossification may not entirely mirror that observed in clinical cases. Therefore, there is an urgent imperative to develop a novel and feasible animal model. Methods: In this study, all the Enpp1 gene deficiency mice (a mouse model with heterotopic ossification of multiple ligaments) were divided into three groups: the control group, the spinal brake group, and the hyperactive group (treadmill training group). An external spinal fixation device was designed to restrict mice's spinal flexion and extension at 6 weeks of age. The brace was adjusted weekly according to the changes in the size of the mice. Additionally, treadmill training was used to increase activity in the spinal ligaments and Achilles tendons of the mice. Micro-CT scanning and HE staining were performed at 12, 20, and 28W to evaluate the degree of ossification in the spinal ligament and Achilles tendon. What's more, As one of the mechanical stimulation transduction signals, YAP plays a crucial role in promoting osteogenic differentiation of cells. Immunofluorescence was utilized to assess YAP expression levels for the purpose of determining the extent of mechanical stimulation in tissues. Results: Our findings showed that a few ossification lesions were detected behind the vertebral space of mice at 8 weeks of age. Spinal immobilization effectively restricts the flexion and extension of cervical and thoracic vertebrae in mice, delaying spinal ligament ossification and reducing chronic secondary spinal cord injury. Running exercises not only enhance the ossification area of the posterior longitudinal ligament (PLL) and Achilles tendons but also exacerbate secondary spinal cord injury. Further immunofluorescence results revealed a notable increase in YAP expression levels in tissues with severe ossification, suggesting that these tissues may be subjected to higher mechanical stimulation. Conclusion: Mechanical stimulation plays a pivotal role in the process of heterotopic ossification in tissues. Our study provided valid animal models to further explore the pathological mechanism of mechanical stimulation in HOTL development. [ABSTRACT FROM AUTHOR]

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Aims: Mechanical stimulation is a key factor in the development and healing of tendon-bone insertion. Treadmill training is an important rehabilitation treatment. This study aims to investigate the benefits of treadmill training initiated on postoperative day 7 for tendon-bone insertion healing. Methods: A tendon-bone insertion injury healing model was established in 92 C57BL/6 male mice. All mice were divided into control and training groups by random digital table method. The control group mice had full free activity in the cage, and the training group mice started the treadmill training on postoperative day 7. The quality of tendon-bone insertion healing was evaluated by histology, immunohistochemistry, reverse transcription quantitative polymerase chain reaction, Western blotting, micro-CT, micro-MRI, open field tests, and CatWalk gait and biomechanical assessments. Results: Our results showed a significantly higher tendon-bone insertion histomorphological score in the training group, and the messenger RNA and protein expression levels of type II collagen (COL2A1), SOX9, and type X collagen (COL10A1) were significantly elevated. Additionally, tendon-bone insertion resulted in less scar hyperplasia after treadmill training, the bone mineral density (BMD) and bone volume/tissue volume (BV/TV) were significantly improved, and the force required to induce failure became stronger in the training group. Functionally, the motor ability, limb stride length, and stride frequency of mice with tendon-bone insertion injuries were significantly improved in the training group compared with the control group. Conclusion: Treadmill training initiated on postoperative day 7 is beneficial to tendon-bone insertion healing, promoting biomechanical strength and motor function. Our findings are expected to guide clinical rehabilitation training programmes. Cite this article: Bone Joint Res 2023;12(5):339–351.

Objective To investigate the effects of treadmill training on the repair of myelin structure of dorsal corticospinal tract (dCST) in mice with T10 spinal cord mild contusion. Methods Twelve adult C57/BL female mice were used to construct and verify the model of spinal cord mild contusion, and another 30 mice were randomly divided into 3 groups (n=10): sham group, spinal cord injury (SCI) group, and treadmill training group.The mice of SCI and treadmill training groups were given unilateral (left) spinal cord contusion, while the sham group was given laminectomy only.A 4-week training scheme was conducted for the treadmill training group 1 week after SCI surgery (parameters: 12 m/min, 30 min/session, 1 time/day, 5 d/week).The primary motor cortex (M1) of mice in each group was injected with biotinylated dextran amine (BDA) to trace dCST 2 weeks before sampling, followed by the collection of tissue samples when the 4-week training finished.Then the expression levels of platelet-derived growth factor receptor α(PDGFRα), Ki67 protein, oligodendrocyte transcription factor 2(Olig2), adenomatous polyposis coli protein (APC/CC1) and myelin basic protein (MBP) were detected by immunofluorescence assay.Transmission electron microscopy (TEM) was also used to observe the myelination in the left dCST area.Moreover, Basso Mouse Scale (BMS) was performed in each group to evaluate the motor function of left hindlimb before injury, 1 week after injury and 1, 2, and 4 weeks after training. Results Immunofluorescent labeling showed that the ratio of PDGFRα/Ki67 double positive cells to the total number of PDGFRα positive cells, the ratio of Olig2/APC/CC1 double positive cells to the total number of Olig2 positive cells, as well as the mean fluorescence intensity of MBP in the left dCST area of the SCI group were significantly lower than those of the sham group (P < 0.01), while these indexes were higher in the treadmill training group than in the SCI group (P < 0.01).TEM results indicated that the G-ratio of the left dCST area was elevated in the SCI group (P < 0.01), but was reduced greatly in the treadmill training group (P < 0.01).Finally, the BMS scores were improved in the treadmill group at each detection time point after injury, but there was no significant difference as compared with the SCI group (P>0.05). Conclusion Treadmill training can facilitate the proliferation and differentiation of oligodendrocytes precursor cells (OPCs), improve the maturation of oligodendrocytes (OLs) in the left dCST region, and increase the expression of myelin related proteins, thus promoting the repair of myelin structure after SCI in adult mice.

In contracting muscles, carbohydrates and fatty acids serve as energy substrates; the predominant utilization depends on the workload. Here, we investigated the contribution of non-mitochondrial and mitochondrial metabolic pathways in response to repeated training in a polygenic, paternally selected marathon mouse model (DUhTP), characterized by exceptional running performance and an unselected control (DUC), with both lines descended from the same genetic background. Both lines underwent three weeks of high-speed treadmill training or were sedentary. Both lines' muscles and plasma were analyzed. Muscle RNA was sequenced, and KEGG pathway analysis was performed. Analyses of muscle revealed no significant selection-related differences in muscle structure. However, in response to physical exercise, glucose and fatty acid oxidation were stimulated, lactate dehydrogenase activity was reduced, and lactate formation was inhibited in the marathon mice compared with trained control mice. The lack of lactate formation in response to exercise appears to be associated with increased lipid mobilization from peripheral adipose tissue in DUhTP mice, suggesting a specific benefit of lactate avoidance. Thus, results from the analysis of muscle metabolism in born marathon mice, shaped by 35 years (140 generations) of phenotype selection for superior running performance, suggest increased metabolic flexibility in male marathon mice toward lipid catabolism regulated by lactate dehydrogenase. [ABSTRACT FROM AUTHOR]

Purpose: Exercise interventions have been shown to increase motor capacities in adolescents with cerebral palsy; however, how they affect habitual physical activity (HPA) and sedentary behavior is unclear. The main objective was to correlate changes in HPA with changes in mobility capacity following exercise interventions. Methods: A total of 54 participants (aged 12–20 y) with bilateral spastic cerebral palsy at Gross Motor Function Classification System (GMFCS) levels II and III received 4 months of group progressive resistance training or treadmill training. Mobility measurements and HPA (averaged over 96 h) were made before and after interventions. Results: Averaged baseline mobility and HPA measures and improvements in each after both interventions were positively correlated in all participants. Percentage of sedentary/awake time decreased 2%, with significant increases in HPA measures of step count (16%), walk time (14%), and upright time (9%). Mobility measures and HPA changes were quite similar between Gross Motor Function Classification System levels, but improvement in HPA after group progressive resistance training was greater than after treadmill training (12% vs 4%) and correlated with mobility improvement. Conclusions: Mobility capacity improved after these interventions and was clearly associated with improved HPA. The group progressive resistance training intervention seems preferable to improve HPA, perhaps related to greater social interaction and motivation provided by group training. [ABSTRACT FROM AUTHOR]

Objective: To systematically summarize and examine current evidence regarding the combination of virtual reality and treadmill training in patients with walking and balance impairments. Data sources: English language randomized controlled trials, participants with walking and balance impairments, intervention group used virtual reality and treadmill, control group only used treadmill with the same training frequency and number of sessions. Six bioscience and engineering databases were searched. Methods: Two independent reviewers conducted study selection, data extraction, and quality assessment. Methodological quality was assessed using the Physiotherapy Evidence Database (PEDro) scale. Results: Sixteen randomized controlled trials including 829 participants were identified. Compared to treadmill-only training, virtual reality augmented treadmill training induced significantly faster walking (p < 0.001; standardized mean difference (SMD) = 0.55, 95%CI: 0.30 to 0.81), longer step length (p < 0.001; SMD = 0.74, 95%CI: 0.42 to 1.06), narrower step width (p = 0.03; SMD = −0.52, 95%CI: −0.97 to −0.06), longer single leg stance period (p = 0.003; SMD = 0.77, 95%CI: 0.27 to 1.27), better functional mobility (p = 0.003; SMD = −0.44, 95%CI: − 0.74 to −0.15), improved balance function (p = 0.04; SMD = 0.24, 95%CI: 0.01 to 0.47), and enhanced balance confidence (p = 0.03; SMD = 0.73, 95%CI: 0.08 to 1.37). Walking endurance did not differ significantly between groups (p = 0.21; SMD = 0.13, 95%CI: −0.07 to 0.34). Conclusions: Virtual reality augmented treadmill walking training enhances outcomes compared to treadmill-only training in patients with walking and balance impairments. The results of this review support the clinical significance of combining virtual reality with treadmill training with level 1A empirical evidence. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to evaluate the effectiveness of various results of treadmill training in children and adults with Down syndrome (DS). Methods: To provide an overview of this effectiveness, we conducted a systematic literature review of studies in which participants with DS from all age groups received treadmill training, alone or combined with physiotherapy. We also looked for comparisons with control groups of patients with DS who did not undergo treadmill training. The search was performed in medical databases: PubMed, PEDro, Science Direct, Scopus, and Web of Science, and included trials published until February 2023. Following PRISMA criteria, the risk of bias assessment was conducted using a tool developed by the Cochrane Collaboration for RCT. The selected studies presented multiple outcomes with differences in methodology; therefore, we were not able to conduct any sort of data synthesis, so we present measures of treatment effect as mean differences and corresponding 95% confidence intervals. Results: We selected 25 studies for the analysis with a total number of 687 participants, and identified 25 different outcomes which are presented in a narrative manner. In all outcomes we observed positive results favoring the treadmill training. Discussion: Introducing treadmill exercise into typical physiotherapy generates improvement in mental and physical health of people with DS. [ABSTRACT FROM AUTHOR]

Obesity exacerbates aging-induced adipose tissue dysfunction. This study aimed to investigate the effects of long-term exercise on inguinal white adipose tissue (iWAT) and interscapular brown adipose tissue (iBAT) of aged obese mice. Two-month-old female mice received a high-fat diet for 4 months. Then, six-month-old diet-induced obese animals were allocated to sedentarism (DIO) or to a long-term treadmill training (DIOEX) up to 18 months of age. In exercised mice, iWAT depot revealed more adaptability, with an increase in the expression of fatty acid oxidation genes (Cpt1a, Acox1), and an amelioration of the inflammatory status, with a favorable modulation of pro/antiinflammatory genes and lower macrophage infiltration. Additionally, iWAT of trained animals showed an increment in the expression of mitochondrial biogenesis (Pgc1a, Tfam, Nrf1), thermogenesis (Ucp1), and beige adipocytes genes (Cd137, Tbx1). In contrast, iBAT of aged obese mice was less responsive to exercise. Indeed, although an increase in functional brown adipocytes genes and proteins (Pgc1a, Prdm16 and UCP1) was observed, few changes were found on inflammation-related and fatty acid metabolism genes. The remodeling of iWAT and iBAT depots occurred along with an improvement in the HOMA index for insulin resistance and in glucose tolerance. In conclusion, long-term exercise effectively prevented the loss of iWAT and iBAT thermogenic properties during aging and obesity. In iWAT, the long-term exercise program also reduced the inflammatory status and stimulated a fat-oxidative gene profile. These exercise-induced adipose tissue adaptations could contribute to the beneficial effects on glucose homeostasis in aged obese mice. [ABSTRACT FROM AUTHOR]

Abstract Optimal exercise can promote the development of cognitive functions. Nevertheless, mechanisms that elicit these positive effects of exercise still need to be elucidated. Insulin‐like growth factor 2 (IGF2) is known to act as a potent enhancer of memory and cognitive functions, whereas the mechanism by which IGF2 regulates cognitive functions in terms of moderate treadmill exercise remains largely vague. In the study, rats were subjected to low‐, moderate‐, and high‐intensity treadmill training for 6 weeks. Then, the Morris water maze test was used to investigate spatial learning and memory ability in rats subjected to treadmill exercises of different intensities. Subsequently, gene chip and bioinformatics analyses were used to explore IGF2 and predict target microRNAs (miRNAs). Quantitative real‐time polymerase chain reaction, western blot, and immunofluorescence analysis were performed to detect the levels of IGF2. Furthermore, IGF2‐small interfering RNA, the miRNA‐483‐mimic, and the miRNA‐483‐inhibitor were transfected to determine the role of IGF2 and miRNA‐483 in the growth of hippocampal neurons. The results of the Morris water maze test showed that moderate‐intensity treadmill training enhanced cognitive functions; meanwhile, the expression of IGF2 was significantly upregulated in the hippocampus after moderate‐intensity treadmill exercise. From databases, miRNA‐483 was screened and predicted as the target gene of IGF2. Moreover, silencing IGF2 inhibited neurite growth in the hippocampus of rats, the miRNA‐483‐inhibitor ameliorated silencing IGF2 induced impairment of hippocampal neurons. These findings suggested that treadmill training could enhance cognitive functions, wherein the underlying mechanism involved an increase in the expression of IGF2 and downregulation of miRNA‐483.

Type 2 diabetes is a major factor contributing to cognitive decline and Alzheimer’s disease (AD). Treadmill running is considered to be a critical approach for mice and rats to lower blood sugar and improve learning and memory capacity. The growth factor receptor-bound protein 10 (Grb10) has been proposed to inhibit insulin signaling and defective brain insulin signaling resulted in the cognitive deficits in patients with AD. However, the positive roles of treadmill training on diabetic- related impaired cognitive function and their molecular mechanisms remain unclear. Here, to investigate whether there was neuroprotective effects of treadmill training on impaired cognitive function caused by diabetes, the rats were injected intraperitoneally with streptozotocin at a dose of 30 mg/kg to establish diabetic model (DM). We found that higher Grb10, BACE1 and PHF10 protein levels in the hippocampus of DM rats, lower phosphorylation IGF-1Rβ and IRS-1(ser307). However, 8 weeks treadmill training effectively reduced abnormal Grb10, enhanced postsynaptic density protein PSD-93, PSD-95, SYN expressions of hippocampus, restored PI3K/Akt/ERK and mTOR/AMPK signaling, thus alleviated spatial learning and memory deficit, compared with DM group. Additionally, treadmill training also increased GLUT4 transportation. Overall, our findings suggest that treadmill intervention improved cognitive impairments caused by diabetes disease partly through modulating Grb10/ PI3K/Akt/ERK as well as mTOR/AMPK signaling.

Background: Motor and cognitive impairments impact the everyday functioning of people with MS (pwMS). The present randomized controlled trial (RCT) evaluated the benefits of a combined motor–cognitive virtual reality training program on key motor and cognitive symptoms and related outcomes in pwMS. Methods: In a single-blinded, two-arm RCT, 124 pwMS were randomized into a treadmill training with virtual reality (TT + VR) group or a treadmill training alone (TT) (active-control) group. Both groups received three training sessions per week for 6 weeks. Dual-tasking gait speed and cognitive processing speed (Symbol Digit Modalities Test, SDMT, score) were the primary outcomes. Secondary outcomes included additional tests of cognitive function, mobility, and patient-reported questionnaires. These were measured before, after, and 3 months after training. Results: Gait speed improved (p < 0.005) in both groups, similarly, by about 10 cm/s. The TT + VR group (n = 53 analyzed per-protocol) showed a clinically meaningful improvement of 4.4 points (95% CI 1.9–6.8, p = 0.001) in SDMT, compared to an improvement of only 0.8 points in the TT (n = 51 analyzed per-protocol) group (95% CI 0.9–2.5 points, p = 0.358) (group X time interaction effect p = 0.027). Furthermore, TT + VR group-specific improvements were seen in depressive symptoms (lowered by 31%, p = 0.003), attention (17%, p < 0.001), and verbal fluency (11.6% increase, p = 0.002). Discussion: These findings suggest that both TT and TT + VR improve usual and dual-task gait in pwMS. Nonetheless, a multi-modal approach based on VR positively impacts multiple aspects of cognitive function and mental health, more than seen after treadmill-treading alone. Trial registered at ClinicalTrials.Gov NCT02427997. [ABSTRACT FROM AUTHOR]

Treadmill exercise is widely considered an effective strategy for restoration of skilled motor function after spinal cord injury (SCI). However, the specific exercise intensity that optimizes recovery and the underlying mechanistic basis of this recovery remain unclear. To that end, we sought to investigate the effect of different treadmill exercise intensities on cortical mTOR activity, a key regulator of functional recovery following CNS trauma, in an animal model of C5 crush spinal cord injury (SCI). Following injury, animals were subjected to treadmill exercise for 4 consecutive weeks at three different intensities (low intensity [LEI]; moderate intensity [MEI]; and high intensity [HEI]). Motor function recovery was assessed by horizontal ladder test, cylinder rearing test, and electrophysiology, while neurotrophic factors and cortical mechanistic target of rapamycin (mTOR) pathway–related proteins were assessed by Western blotting. The activation of the cortical mTOR pathway and axonal sprouting was evaluated by immunofluorescence and the changes of plasticity in motor cortex neurons were assessed by Golgi staining. In keeping with previous studies, we found that 4 weeks of treadmill training resulted in improved skilled motor function, enhanced nerve conduction capability, increased neuroplasticity, and axonal sprouting. Importantly, we also demonstrated that when compared with the LEI group, MEI and HEI groups demonstrated elevated expression of brain-derived neurotrophic factor (BDNF), insulin-like growth factor 1 (IGF-1), phosphorylated ribosomal S6 protein (p-S6), and protein kinase B (p-Akt), consistent with an intensity-dependent activation of the mTOR pathway and neurotrophic factor expression in the motor cortex. We also observed impaired exercise endurance and higher mortality during training in the HEI group than in the LEI and MEI groups. Collectively, our findings suggest that treadmill exercise following SCI is an effective means of promoting recovery and highlight the importance of the cortical mTOR pathway and neurotrophic factors as mediators of this effect. Importantly, our findings also demonstrate that excessive exercise can be detrimental, suggesting that moderation may be the optimal strategy. These findings provide an important foundation for further investigation of treadmill training as a modality for recovery following spinal cord injury and of the underlying mechanisms. [ABSTRACT FROM AUTHOR]