Stroke is one of the leading causes of death globally. Advancements in medical science and technology have contributed to a reduction in the mortality rate among individuals who have experienced a stroke. The present study presents findings from a single case report employing a single-subject research design. To achieve optimal rehabilitation outcomes, Functional Electrical Stimulation (FES) was incorporated with Treadmill Training (TT), accompanied by challenging tasks during physiotherapy. Hereby, the authors present a case report of a 66-year-old male post-stroke patient with left-sided weakness, impaired grip strength, and mobility issues following a right Middle Cerebral Artery (MCA) ischaemic stroke. His medical history includes type 2 diabetes mellitus and systemic hypertension, with no significant family medical history reported. The patient presented with notable motor deficits and functional limitations resulting from the right MCA ischaemic stroke. Interventions targeting spasticity reduction, muscle strengthening, endurance, and gait retraining were essential to improve the patient’s functional mobility and overall quality of life. The findings revealed significant improvement in various outcome measures, including the Modified Ashworth Scale (MAS), Voluntary Motor Control (VMC), Dynamic Gait Index (DGI), Berg Balance Scale (BBS), and Functional Independence Measure (FIM), indicating positive changes and enhanced quality of life in stroke survivors. The cumulative effect of FES and TT with challenging tasks can significantly improve gait, muscle strength, and balance in patients recovering from stroke.

Cerebral palsy (CP) is a non-progressive neurological disorder that impairs motor control and coordination due to brain injury or abnormalities before, during, or shortly after birth. Although robotic gait training can improve overall gait patterns in CP, interventions targeting the 'foot rockers' motion, essential for stable weight transfer and effective push-off, have received limited attention. In this study, five adults with CP were recruited to train on a robotic treadmill system in which controlled downward forces were applied to the pelvis during walking, promoting implicit motor learning to develop an improved foot rockers strategy. Following this, during overground walking, participants received distinct real-time auditory cues at heel strike and push-off, providing self-awareness feedback to reinforce and maintain the foot rockers pattern acquired during treadmill training. Post-training analyses reported increased Tibialis Anterior activation during early stance, enhancing dorsiflexion and heel strike, and greater Soleus and Gastrocnemius engagement in late stance for stronger push-offs (p <0.05). These functional gains were reflected in key spatiotemporal metrics: longer step length, greater toe clearance, a reduced stance percentage, and a shorter double stance time (p <0.05). Participants also exhibited increased range of motion of the foot and increased knee and hip extension throughout stance, reflecting a more upright lower limb (p <0.05). Survey responses confirmed that participants acknowledged the resistive treadmill training for strengthening their muscles and influencing their walking patterns, and reported that the auditory biofeedback enhanced their awareness of heel-to-toe contact. Participants emphasized the necessity of incorporating both interventions, highlighting its potential as a promising approach to improving foot rockers and overall gait pattern in adults with CP.

Combining automated mechanical peripheral stimulation and treadmill exercise for gait rehabilitation in Parkinson's disease: A randomized controlled trial.

Aerobic exercise improves the high-fat diet/streptozotocin-induced depression-like behaviors by reducing hippocampal neuroinflammation through suppressing the BTK/NF-κB signaling pathway.

Background. Anterior cruciate ligament (ACL) reconstruction is frequently associated with persistent quadriceps weakness and reduced quality of life. Graded backward treadmill walking has emerged as a promising intervention to enhance neuromuscular rehabilitation. Objective. To investigate the effects of graded backward treadmill training on quadriceps strength, quadriceps muscle mass, and quality of life in individuals after ACL reconstruction. Methodology. Sixty participants (aged 18–45 years) who underwent ACL reconstruction using a semitendinosus graft were randomly assigned to five groups (A–E; n = 12 per group). Groups A–D performed backward treadmill walking at inclinations of 0°, 5°, 10°, and 15°, respectively. Group E served as the control group and received conventional rehabilitation. Training was conducted for 20 minutes per session, three days per week, for four weeks. Outcome measures included quadriceps strength (assessed using a dynamometer), quadriceps muscle mass (assessed by ultrasound), and quality of life (measured using the IKDC and ACL-QOL questionnaires). Statistical analyses were performed using analysis of variance (ANOVA) and non-parametric tests. Results. All groups demonstrated improvements in quadriceps strength, muscle mass, and quality of life following the intervention. Group B exhibited the greatest mean improvement in quadriceps strength, whereas Group D showed the largest increases in quadriceps muscle mass and quality of life scores. Significant between-group differences were observed at baseline for quadriceps strength (p &lt; 0.001) and at post-test for ultrasound-derived muscle mass (p = 0.010), IKDC scores (p = 0.033), and ACL-QOL scores (p = 0.016). Discussion. The findings indicate that backward treadmill training led to improvements in quadriceps strength, muscle mass, and quality of life across all intervention groups. The superior strength gains observed in Group B suggest that moderate incline backward walking may be optimal for enhancing force production, whereas the pronounced increases in muscle mass and quality of life in Group D indicate that higher inclinations may be particularly effective for promoting muscular hypertrophy and psychosocial recovery. Conclusion. Graded backward treadmill training following ACL reconstruction improves quadriceps muscle mass and quality of life, with higher inclinations showing greater effects. Further research is warranted to determine long-term outcomes and to identify optimal training parameters.

Approximately one-third of older adults fall each year, most often due to slips or trips. Fall incidence is even higher in those with cognitive impairment (CI). Among older adults who fall, about 50% are unable to get up without assistance. Such unrecovered falls are particularly critical, as they are linked to prolonged lying periods, an increased risk of medical complications, and mortality. As unrecovered falls require third-party assistance, they offer an opportunity to incorporate proxy information into fall reporting to reduce recall bias. Perturbation-based balance training (PBT) aims to improve recovery reactions in response to balance disturbances such as slips and trips and thereby prevent falls. This task-specific approach has shown promise in reducing falls in low-risk older adults. However, its efficacy in high-risk populations, especially in participants with CI, remains largely unknown. The primary aim of the TRAIL study is to evaluate the efficacy of treadmill PBT in reducing unrecovered falls among fall-prone older adults with and without CI. In this multi-center, assessor-blinded, randomized controlled parallel-group trial, 396 older adults (≥ 70 years) at risk of falling (≥ 40% prospective fall risk, Timed Up and Go ≥ 10s) will be assigned (1:1) to receive nine sessions of either treadmill PBT or conventional treadmill training (CTT) over three weeks. The primary outcome is the incidence of unrecovered falls within twelve months post-intervention, tracked via monthly fall calendars, phone interviews, proactive reporting, and proxy information. Secondary outcomes include other fall-related outcomes (e.g. total falls, injurious falls, falls per physical activity), physical capacity and activity, psychological status, and cognitive functioning. Assessments will be conducted at baseline, post-intervention, as well as six and twelve months after the intervention. Primary analyses will follow the intention-to-treat principle. Treadmill PBT is expected to reduce unrecovered falls by ≥ 50% over twelve months, compared to CTT. If effective, the low-volume PBT approach can serve as an important treatment option for the rapidly growing group of fall-prone older adults, especially those with CI, for whom evidence-based strategies for fall prevention remain limited. Prospectively registered at ClinicalTrials.gov (NCT06652828). First posted: 2024-10-22, last update posted: 2025-05-14.

Aging is accompanied by progressive impairments in mitochondrial bioenergetics, apoptosis regulation, and gut microbiota homeostasis, all of which contribute to cognitive decline. In this study, we investigated whether the effects of treadmill exercise on the gut microbiota-mitochondrion-neuronal plasticity axis differed between young (15 months) and old (28 months) mice. Male C57BL/6 mice were randomly assigned to the following groups: early sedentary, early exercise, late sedentary, or late exercise groups and completed an 8-week treadmill training protocol. Cognitive function was assessed using the passive avoidance test and the Morris water maze test. Hippocampal mitochondrial respiration, Ca2+ retention capacity, and Bax/Bcl-2 expression were quantified, and the gut microbiota composition was analyzed using 16S ribosomal RNA sequencing. Mice that did not exercise in old age exhibited memory impairment, decreased mitochondrial oxidative respiration, reduced Ca2+ retention, increased Bax expression, decreased Bcl-2 levels, and decreased abundance of Lactobacillus, Bifidobacterium, and Akkermansia. Exercise significantly improved behavioral performance, mitochondrial function, and apoptosis balance, while also increasing beneficial gut microbiota. Notably, these effects were significantly greater in late-aged compared to early-aged mice. These results demonstrate that the efficacy of exercise in modulating the microbiota-mitochondrion-brain axis varies with age. Early-aged appears to represent a more responsive biological period during which exercise is more effective in improving mitochondrial integrity, microbiota composition, and cognitive resilience. These results suggest that initiating exercise early in the aging process may maximize neuroprotective effects and delay age-related functional decline.

Myocardial infarction (MI) often induces acute kidney injury (AKI) via systemic hypoperfusion and oxidative stress, yet the protective mechanisms of exercise remain unclear. This study investigated whether intermittent exercise alleviates MI-induced AKI through the insulin-like growth factor-1 (IGF-1)/PI3K/AKT signaling pathway. An AKI model was established in mice via coronary artery ligation, followed by moderate-intensity intermittent treadmill training for 4 weeks. Echocardiography, serum biochemical markers, renal histology, RT-qPCR, and Western blotting were used to assess cardiac and renal function, inflammatory cytokines, oxidative stress, apoptosis, and IGF-1/PI3K/AKT signaling. In vitro, H2O2-treated NRK renal cells were used to mimic oxidative damage. Recombinant human IGF-1 (rhIGF-1), AMPK agonist AICAR, IGF-1 receptor inhibitor NVP-AEW541, and PI3K inhibitor LY294002 were applied to explore the pathway’s involvement in exercise-induced renoprotection. MI led to impaired cardiac function, renal structural injury, elevated BUN and MDA levels, increased expression of IL-6, TNF-α, Bax, and Cleaved Caspase-3, and decreased SOD activity. Intermittent exercise improved cardiac output, attenuated renal injury, enhanced antioxidant capacity, and upregulated IGF-1 expression and its downstream PI3K/AKT signaling. In vitro, rhIGF-1 and AICAR mimicked the protective effects of exercise, while IGF-1R or PI3K inhibitors partially abolished these effects. These findings suggest that intermittent exercise ameliorates MI-induced AKI by activating the IGF-1/PI3K/AKT pathway, thereby exerting anti-inflammatory, antioxidant, and anti-apoptotic effects. This study highlights the role of exercise-induced IGF-1 in heart-kidney axis protection and provides a mechanistic basis for therapeutic interventions targeting MI-related renal complications.

Age-related obesity is a growing healthcare burden. Effectiveness of body weight reducing mediators changes with aging and these alterations may contribute to aging obesity. Our previous results suggested a potential contributions of urocortin 2 (UCN2) to aging obesity and age-related cachexia. Lifestyle interventions, such as caloric restriction or physical activity can improve body weight and body composition. Previous observations suggest that lifestyle interventions may also influence age-associated regulatory changes in energy balance. We aimed to study the effects of a 12-week treadmill training or caloric restriction on the central hypermetabolic responsiveness to UCN2 in middle-aged 6- and 12-month old male Wistar rats. Interventions started at age 3- or 9-months. Following the interventions, acute hypermetabolic/hyperthermic responses were tested upon intracerebroventricular injections of UCN2. Both the training and the caloric restriction lead to weight loss and training led to favorable body composition changes. UCN2-induced hypermetabolism/hyperthermia was diminished by both interventions in both age-groups. The Ucn2 mRNA expression detected by RNAscope in situ hybridization in the hypothalamic paraventricular nucleus was also decreased by both interventions. UCN2-induced hypermetabolism/hyperthermia in the trained and caloric restricted middle-aged groups resembled those of young adult 3-month rats. Lifestyle interventions appear to delay age-related regulatory alterations of energy balance.

Objective: Hospitalized adults are at risk for decline in physical function, which is pronounced in patients suffering from critical illness. Barriers to early physical therapy and ambulation have been identified, including inadequate staffing and logistical constraints. Bedside treadmill training is an intervention that potentially mitigates these barriers; however, literature on this intervention is lacking. Methods: In this quality improvement project, adult inpatients were treated by physical therapists using portable treadmill training in intensive, progressive, and general care units. Data regarding safety events, resource requirements, indications, and patient acceptability were collected from April 2019 to April 2020. Results: Seventy-seven adult inpatients performed a total of 158 treadmill training sessions. One adverse event and one episode of treadmill device malfunction occurred. Most sessions were performed in intensive (42.4%) or progressive care (30.4%) units. Leading indications identified by treating therapists included respiratory support and isolation precautions, with 19% of all sessions involving patients actively receiving mechanical ventilation. Seventy-five percent of all encounters required only the single treating physical therapist. Conclusions: Portable treadmill training is a feasible and safe approach to facilitate ambulation-based interventions during physical therapy for hospitalized patients. This includes those who are critically ill, require invasive support or monitoring devices that may impede ambulation, and/or require additional staff members in addition to a physical therapist to implement. Clinical situations in which strict isolation, staffing, and/or logistical barriers are present, such as COVID, may benefit the most from bedside treadmill interventions. Impact Statement: Implementation of portable bedside treadmill training into physical therapist practice may improve the performance of ambulation interventions in hospitalized patients. The utility of this form of training is highlighted in clinical scenarios in which logistical or environmental barriers exist.

Abstract Although selective androgen receptor modulators (SARMs) are not yet approved for clinical use, their anabolic potential has led to widespread usage among amateur bodybuilders seeking increased muscle mass. Given their tissue-selective anabolic and metabolic actions, SARMs may also influence physiological adaptations relevant to endurance training, such as energy metabolism and recovery. This study investigated the effects of two SARMs, ostarine and ligandrol, and their interaction with endurance training, on metabolic markers and sleep duration in healthy male rats. The study was organised in two 8-week experiments. The rats were randomised into four groups per each experiment – two undergoing treadmill training and two sedentary. In the first experiment, one sedentary and one trained group received ostarine, while in the second, one sedentary and one trained group were administered ligandrol. Control experimental groups received only vehicle. Metabolic indices and sleep were assessed using Comprehensive Laboratory Animal Monitoring System chambers. Neither SARMs nor endurance training significantly affected resting oxygen consumption, energy expenditure, respiratory exchange ratio, or food intake. However, both ostarine and ligandrol significantly prolonged sleep duration. These findings suggest that SARMs may modulate recovery-related processes such as sleep, even in the absence of major metabolic alterations. The combination of SARMs and training did not yield additional effects beyond those of SARMs alone. While non-steroidal SARMs did not alter resting metabolic indices, they significantly increased sleep duration. Endurance training, alone or combined with SARMs, did not significantly impact the studied parameters.

Sex‐related physiological differences influence health, disease, and responses to preventive interventions. We aimed to compare the effects of exercise training on cardiovascular autonomic modulation and oxidative stress in target organs, focusing on sex differences. Wistar rats were distributed into sedentary male (SM) and female (SF), and trained male (TM) and female (TF) groups. Arterial pressure was recorded intra‐arterially, and autonomic modulation was assessed. Rats underwent treadmill training (5 days/week, 8 weeks). Oxidative stress was evaluated in cardiac and renal tissues. There were sex‐related differences in anthropometric, functional, autonomic, and oxidative stress markers. In turn, aerobic exercise training led to significant enhancements in functional performance, cardiovascular autonomic control, and oxidative stress status. Notably, these benefits were more evident in females. Vascular sympathetic modulation correlated positively with renal lipid peroxidation (LPO). Cardiac LPO was lower in TM, SF, and TF (vs. SM). Only TF showed reduced renal LPO and improved cardiac redox balance. Trained females also demonstrated greater improvements in renal antioxidant capacity (TRAP: ~1.6 times), cardiac oxidized glutathione (~3.3 times) (vs. TM), and increased nitrite concentration (~2.1 times) (vs. SF). In conclusion, female rats exhibited greater improvements in cardiovascular autonomic modulation and oxidative profile in target organs in response to exercise training compared to male rats.

Effects of dual-task training on gait variability in individuals with Parkinson's disease: A randomized controlled trial.

Depression is more prevalent among women, and while aerobic exercise serves as an effective nonpharmacological intervention, the potential mechanisms underlying its antidepressant effects remain incompletely understood. In basic research, chronic unpredictable mild stress (CUMS) is a widely used model of depression. In recent years, the cGAS-STING pathway has been demonstrated to be associated with depression as a component of innate immunity and a key driver of neuroinflammation. However, whether this pathway mediates the antidepressant effects of aerobic exercise remains to be elucidated. In this study, 36 female C57BL/6 mice were divided into a control group, a CUMS group, and a CUMS plus exercise group (CUMS + EX), with the CUMS + EX group undergoing a six-week treadmill training program. A multimodal approach was used, integrating behavioural assessment, hippocampal histopathological analysis, and molecular analysis of neuroinflammatory pathways, neurotransmitters, and sex hormones. The findings revealed that exercise intervention significantly ameliorated CUMS-induced depressive-like behaviour in female mice. This improvement was accompanied by reduced hippocampal neuronal damage, suppressed glial cell activation, and decreased levels of proinflammatory cytokines (IL-6, IL-1β, TNF-α). Furthermore, it restored the homeostasis of monoamine neurotransmitters (5-HT, DA, and NE) and regulated the imbalance of serum sex hormones. Mechanistically, exercise significantly suppressed the activation of the cGAS-STING signalling pathway and downregulated key proteins in the NF-κB pathway. In summary, our findings indicate that aerobic exercise alleviates depressive-like behaviour in female mice by inhibiting a cascade of responses triggered by neuroinflammation mediated through the hippocampal cGAS/STING/NF-κB pathway. These findings provide novel mechanistic insights into the antidepressant effects of exercise and suggest that the cGAS-STING pathway may serve as a therapeutic target.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-29325-3.

A role for INPP5D in aerobic exercise-mediated attenuation of microglial activation and neuroinflammation in Alzheimer's disease.

BackgroundExercise offers neuroprotective and cognitive benefits against neurodegeneration in Alzheimer's disease, hypothesized to be due to the secretion of signaling molecules known as brain‐targeting exerkines. However, the responsiveness of these exerkines across multiple organs remains poorly understood.MethodWe leveraged the publicly available (MoTrPAC) dataset. Rats aged 6 months underwent a progressive treadmill training protocol. Blood (cells and plasma) and 18 solid tissues such as brain (cortex, hippocampus, hypothalamus) were collected, and multi‐omics analyses were performed on them. We examined the protein and transcriptional expression of several brain‐targeting exerkines across all collected tissues.ResultBrain‐targeting, tissue‐specific exerkine responsiveness ranked as follows: prosaposin > cathepsin B > Clusterin = FNDC5/irisin > platelet factor 4 > brain‐derived neurotrophic factor (BDNF) = Gpld1. However, both the protein and transcriptional expression of all these brain‐targeting exerkines remained unchanged in the brain across males and females throughout all 8 weeks of treadmill training.ConclusionContrary to previous studies, our analysis shows that brain‐targeting exerkines remained unchanged in the brain after exercise, challenging the notion of a body‐brain exerkine axis and questioning its role in neuroprotection and cognitive benefits.

SummaryAlthough its effectiveness and underlying mechanisms are not fully understood, regular physical exercise (PE) is a potential low-cost strategy to prevent or delay neurodegeneration. Plasma neurofilament light chain (NfL), an established biomarker of axonal damage, helps monitor the progression of neurodegenerative disease. Here, we tested whether moderate-intensity endurance exercise modulates body weight trajectories in a rat model of tauopathy expressing human truncated tau protein (WKY72) and how it is associated with plasma NfL. Three months old Wistar Kyoto (WKY) and tauopathic WKY72 rats underwent 10 weeks long treadmill training regimen (30 min/day, 5 days/week). NfL was quantified in plasma of experimental animals collected before the experiment, then after 4 and 8 weeks long training. Sedentary controls were tested in parallel. Body weights were recorded at the same intervals and additionally two weeks later. We found that sedentary WKY72 rats displayed a significant 8.9-fold increase in NfL, while trained WKY72 animals showed only a 3.8-fold increase (both p < 0.0001). In WKY rats, exercise paradoxically led to a modest yet significant increase in NfL (2.9-fold, p < 0.001). Moreover, PE prevented the late-stage weight loss observed in sedentary tauopathic rats. In conclusion, moderate-intensity endurance exercise attenuates plasma level of NfL in tauopathic rats, indicating the potential of exercise as a disease-modifying intervention. Our findings establish a framework for further mechanistic exploration of links between PE and neuroprotective processes.

Mechanism by which 24-week different-volume high-intensity interval training ameliorates renal fibrosis in naturally aging rats via regulating the TGF-β1/Smad pathway.

BackgroundSpinal cord injury (SCI) remains a global challenge due to limited neural regeneration and functional recovery. Emerging therapies, such as mesenchymal stem cell-derived exosomes and exercise training, have shown promise, but their individual efficacy is insufficient. The synergistic effects of menstrual blood-derived mesenchymal stem cell-derived exosomes (MenSCs-Exo) and weight-supported treadmill training (WSTT) in SCI repair remain unclear. This study investigated their combined therapeutic potential and underlying mechanisms in SCI rats.MethodsA T10 spinal cord hemisection model was conducted in adult male Sprague-Dawley rats, which were randomized into five groups: Sham, SCI, Exo (200 µg MenSCs-Exo via tail vein injection every 48 h for 4 doses), TT (WSTT starting on day 3 post-SCI), and Exo + TT. Motor function was evaluated using the Basso, Beattie, and Bresnahan (BBB) scale and CatWalk XT® gait analysis. Histological assessments included hematoxylin and eosin (H&E) staining, Masson’s trichrome staining, immunofluorescence for β-tubulin III (Tuj1) and myelin basic protein (MBP), and transmission electron microscopy (TEM). Western blot analyzed fibrosis-related proteins (COL1, COL3, α-SMA) and PI3K/AKT pathway activation (p-AKT, PI3K, β-catenin, LEF1).ResultsCombined Exo + TT significantly improved motor function compared to monotherapies. BBB scores in the Exo + TT group were higher than SCI controls from day 7, with marked differences at 4 weeks (P < 0.05). CatWalk analysis revealed enhanced hindlimb coordination, reduced dragging, and improved paw print parameters in Exo + TT rats. Histologically, Exo + TT reduced spinal cord cavitation, inflammation, and fibrosis (P < 0.01 vs. SCI), while promoting axonal (Tuj1) and myelin (MBP) regeneration with ordered structure. TEM showed preserved myelin lamellae and reduced axonal degeneration. Western blot confirmed decreased COL1, COL3, and α-SMA expression, along with upregulated p-Akt, PI3K, β-catenin, and LEF1 in Exo + TT rats (P < 0.01).ConclusionMenSCs-Exo combined with WSTT synergistically enhances motor recovery after SCI by promoting tissue repair, reducing fibrosis, and activating the PI3K/Akt pathway. This cell-free therapy paired with rehabilitation exercise offers a novel strategy for SCI treatment.Graphical abstractSupplementary InformationThe online version contains supplementary material available at 10.1186/s13287-025-04794-5.

Background: The purpose of the research was to compare the effect of two types of aerobic exercise—with and without incline—on the modulation of oxidative stress and kidney function in chronic kidney disease (CKD) mice. Methods: A total of 24 two-month-old female C57b16 mice weighing 25±26.1 grams, were randomly divided into four groups: healthy control, CKD-affected mice, CKD mice undergoing aerobic exercise without incline, and CKD mice undergoing aerobic exercise with incline. To induce CKD, they received adenine powder at a concentration of 0.2% mg/kg for four weeks. The training groups performed eight weeks of treadmill training (five sessions per week), whit one group exercising on a 20-degree incline and the other on a zero-degree incline. After the last training session, blood samples were collected to measure blood urea nitrogen, urea and glutathione concentration using the ELISA method. The expression levels of the SIRT1, NRF1 and TNF-α genes were measured using qPCR (Real-Time PCR) technique. For statistical analysis, a one-way ANOVA test and Tukey's post hoc test were employed, with a significance level set at P≤ 0.05. Results: The results showed that the induction of CKD caused a significant increase in blood urea nitrogen and a significant decrease in glutathione concentration compared to the healthy control group (P&lt; 0.05). Conversely, in the exercise groups, there was a significant increase in glutathione concentration and a significant decrease in blood urea nitrogen (P&lt; 0.05). The expression level of SIRT1 and NRF1 in the slope training group increased significantly, while the expression level of TNF-α decreased significantly (P&lt; 0.05). Conclusion: Exercises performed on an incline moderates oxidative stress through the TNFα/SIRT1/NRF1 signaling pathway, improving glutathione concentration and blood urea nitrogen levels in mice with chronic kidney disease. Furthermore, the effects of incline exercise were found to be superior to those of exercise without incline.