PURPOSE:The Fugl-Meyer assessment (FMA) is the gold standard for evaluating sensorimotor-impairment after stroke, yet no validated Chinese translation exists despite China's large stroke burden. This study aimed to develop and validate a Chinese version of the FMA for use in Chinese-speaking stroke populations. METHODS:We followed internationally accepted guidelines for translation and cross-cultural adaptation to ensure conceptual, semantic, and cultural equivalence. The process involved forward and backward translation, expert team review, and cognitive pretesting. The finalized Simplified Chinese FMA was administered to 60 adult stroke survivors (subacute and chronic) from rehabilitation centers in Chongqing, China. Psychometric evaluation was cross-sectional and included internal consistency (Cronbach's α), inter-rater reliability (ICC), item-level agreement, concurrent validity (NIHSS, mRS, FIM), and construct validity using factor analysis. RESULTS:The Chinese FMA showed excellent internal consistency (α = 0.770-0.970) and outstanding inter-rater reliability (ICC = 0.99 for both extremities), with item-level agreement of 95% (upper limb) and 93.33% (lower limb). Concurrent validity was confirmed via strong correlations with the mRS (r=-0.534), NIHSS (r=-0.856), and FIM (r = 0.867). Factor analysis supported its theoretical structure, with no ceiling or floor effects observed. CONCLUSIONS:The Chinese FMA demonstrates robust psychometric properties comparable to the original English version and other validated translations.
IntroductionLow-load resistance training [≤50% one-repetition maximum (1-RM)] produces modest hypertrophic adaptations in untrained individuals. Blood flow restriction (BFR) training, combining low mechanical loads (30–40% 1-RM) with proximal limb occlusion, may augment these adaptations by inducing metabolic stress comparable to higher-load exercise. However, evidence comparing low-load multi-component training with and without BFR in physically inactive young adults remains limited. This study examined whether adding BFR to a standardized low-load training program enhances muscle thickness and functional performance outcomes compared with the same program performed without BFR.MethodsIn this single-blind randomized controlled trial conducted at Chongqing Medical University from November 2024 to November 2025, we enrolled 48 physically inactive physically inactive university-aged adults (25 males; mean age 18.98 ± 0.64 years). Participants were randomly assigned (1:1) to receive either low-load multi-component with BFR (n=24) or low-load multi-component without BFR) (n=24) training for 6 weeks (4 sessions/week). The BFR group trained at 30% (weeks 1-3) to 40% (weeks 4-6) 1-RM, with pneumatic cuffs inflated to 50% of individual arterial occlusion pressure. Outcomes were muscle thickness (ultrasound), and physical fitness tests.ResultsAll 48 participants (mean age 19.0 ± 0.6 years) completed the 6-week intervention with ≥85% session attendance. The BFR group demonstrated significantly greater muscle thickness increases compared with without-BFR group in bilateral biceps brachii (right: +0.45 cm vs +0.11 cm, P = 0.001, ηp2=0.20; left: +0.37 cm vs +0.10 cm, P = 0.001, ηp2=0.21) and right rectus femoris (+0.13 cm vs +0.02 cm, P = 0.001, ηp2=0.17). Functional performance improvements favoring BFR included left-hand grip strength (+3.63 kg vs +1.09 kg, P = 0.001, ηp2=0.28), bilateral thigh circumference (P = 0.001, ηp2=0.12), and exercise-specific core training (males: pull-ups +5.92 vs +2.08 repetitions; females: abdominal curls +11.18 vs +3.33 repetitions). Between-group differences reached significance for 10 of 18 primary and secondary outcomes (56%). Seven BFR participants (29%) reported minor, transient discomfort during week 1; no serious adverse events occurred.ConclusionAdding BFR to low-load multi-component training produced greater improvements in limb muscle thickness and functional performance compared with the same training performed without BFR in physically inactive young adults over 6 weeks. Benefits were most evident in upper extremity hypertrophy and task-specific functional capacity, with 56% of outcomes demonstrating significant between-group differences favoring BFR. The intervention was well-tolerated with no serious adverse events. These findings support BFR-enhanced low-load training as a potential alternative for individuals unable or unwilling to engage in high-load resistance training, though generalizability to other populations and longer-term sustainability require further investigation.Clinical Trial Registrationhttps://www.thaiclinicaltrials.org/, identifier TCTR20241110003.
The cognitive impairment resulting from stroke is purported to be associated with impaired neuronal structure and function. Transcranial Magnetic Stimulation (TMS) modulates neuronal or cortical excitability and inhibits cellular apoptosis, thereby enhancing spatial learning and memory in middle cerebral artery occlusion/reperfusion (MCAO/R) rats. In this study, we aimed to investigate whether Sterile alpha and Toll/interleukin receptor motif-containing protein 1 (SARM1), a pivotal Toll-like receptor adaptor molecule and its related mechanisms are involved in the ameliorating effect of TMS on cognitive function post-cerebral ischemia. We evaluated hippocampal injury in MCAO/R rats after one week of treatment with 10-Hz TMS at an early stage. The effect of SARM1 was more effectively assessed through lentivirus-mediated SARM1 overexpression. Various techniques, including FJB staining, HE staining, western blot, immunofluorescence, imunohistochemistry, and transmission electron microscopy, were employed to investigate the molecular biological and morphological alterations of axons, myelin sheaths and apoptosis in the hippocampus. Ultimately, Morris Water Maze was employed to evaluate the spatial learning and memory capabilities of the rats. We observed that TMS significantly reduced the levels of SARM1, NF-κB, and Bax following MCAO/R, while elevating the levels of HSP70, Bcl-2, GAP-43, NF-200, BDNF, and MBP. Overexpression of SARM1 not only reversed the neuroprotective effects induced by TMS but also exacerbated spatial learning and memory impairments in rats. Our results demonstrate that TMS mitigates hippocampal cell apoptosis via the SARM1/HSP70/NF-κB signaling pathway, thus fostering the regeneration of hippocampal axons and myelin sheaths, as well as the improvement of spatial learning and memory.
Regeneration of the corticospinal tract (CST) is considered a therapeutic target to achieve improved recovery of motor function after spinal cord injury (SCI), which is an incurable CNS damage that affects millions of people. Exercise training is effective in improving multiple functions in spinal cord-injured patients. However, the effects of exercise training on axon regeneration have not been sufficiently reported. Osteopontin (OPN) has great potential application as a neuroprotective agent for the repair of the nervous system. Studies have shown that the extent of axon regeneration strongly correlates with the expression of OPN. Our previous studies demonstrated that treadmill exercise supplemented by OPN enhances motor function recovery, but axon regeneration is still limited. Extending the treadmill exercise for 12 weeks, we observed promoted axon regeneration, motor function improvement, and signaling pathway activation in mice with SCI after supplementing OPN. Axon regeneration was observed with an anterograde tracer, motor function recovery was evaluated by animal ethology and electrophysiology, and the levels of IGF-1R/Akt/mTOR signaling pathway were evaluated. The results showed that the CST of C5 crushed mice regenerated and formed synaptic connections with neurons after treadmill exercise supplemented by OPN, the horizontal ladder and cylinder rearing test of injured limbs were improved, motor evoked potential also suggested enhanced nerve conduction, and the expression of p-IR, p-Akt, and p-S6 were increased. And the improvements were more obvious than that of the exercise group. Collectively, our study found that treadmill exercise supplemented by OPN promote axon regeneration and motor function through the IGF-1R/Akt/mTOR signaling pathways, and these improvements can be inhibited by rapamycin and Methyl-beta-CD (M-B-CD).
Acute and chronic exposure to high altitude causes multiple negative neurological consequences. Further research has shown the efficacy of targeted drugs after acute hypoxia. However, the effects and mechanisms of physical therapy like exercise, on after exposed-induced myelin repair and functional improvements have remained unclear. Here, we explored the efficacy of treadmill training at different intensities on recovery in a rat model of acute hypobaric hypoxia (HH) injury. A 4-week treadmill training scheme was used at 30
Background and objectiveStroke often causes gait and balance impairments due to disrupted neural control. While robotic-assisted gait training (RAGT) improves motor function, combining it with low-frequency transcranial magnetic stimulation (LF-rTMS) may enhance neuroplasticity and recovery. This pilot RCT investigates the feasibility and synergistic effects of RAGT + LF-rTMS on gait and balance in stroke patients.Materials and methodsThis pilot RCT included 21 stroke patients randomized into three groups: RAGT + active LF-rTMS, RAGT + sham rTMS, and control (standard physiotherapy). RAGT used an exoskeleton with adjustable speed (0.8–1.8 km/h) and body-weight support (40–60%). LF-rTMS (1 Hz, 80% RMT) targeted the unaffected hemisphere’s M1. Outcomes included 3D gait analysis (spatiotemporal metrics), dynamic balance (COP sway), and clinical scales (FMA-LE, BBS, MMT).ResultsThe RAGT+TMS group demonstrated more improvements in balance (BBS: Δ22.58 vs. Δ15.40 in RAGT+sham TMS; p = 0.05) and motor function (FMA: Δ5.86 vs. Δ1.61; p = 0.04) compared to other groups. Gait analysis revealed significant left step length increases in RAGT+TMS (Δ6.86 cm, p = 0.04), while balance metrics showed reduced postural sway (oscillation length: Δ − 25.01 cm, p = 0.04). All groups improved temporally (p < 0.01), but RAGT+TMS yielded synergistic enhancements in functional recovery.ConclusionThis study demonstrates that combined RAGT and LF-rTMS significantly enhances post-stroke motor recovery, yielding clinically superior improvements in balance (BBS), gait symmetry, and postural control compared to RAGT alone or conventional therapy. The synergistic effects highlight TMS’s potential to augment neuroplasticity when paired with robotic training. While further large-scale trials are needed, these findings support integrating dual-modality approaches for comprehensive stroke rehabilitation.Clinical trial registrationhttps://www.chictr.org.cn/indexEN.html, ChiCTR2200066978.
BACKGROUND:Blood flow restriction creates a state with increased motor function that permits treatment modalities to induce muscle hypertrophy. Blood flow-restricted exercise training (BFRET) may induce motor learning and boost the facilitatory effect of exercise training (ET). OBJECTIVE:This study investigated the effects of BFRET on post-stroke hemi paretic lower extremity function and walking capacity recovery. METHODOLOGY:This randomized clinical trial was conducted from September 2021 to October 2022 at the Department of Rehabilitation Medicine of the Second Affiliated Hospital of Chongqing Medical University in China. Participants were randomized 1:1 to BFRET or ET, each involving 30 minutes of training twice per day for 4 weeks. MAIN OUTCOMES MEASURES:The main outcomes were manual muscle testing (MMT) and Fugl-Meyer assessment scale-lower extremity (FMA-LE), the timed up and go test (TUGT), Outcomes were assessed by blinded raters after 4 weeks of training. RESULTS:40 participants mean [SD] age 48.79[12.58] years, 30 males [75%], 20 were randomized to BFRET and 20 to ET. The mean (SD) time since stroke was 2.5 (1.3) years. The MMT scores showed greater strength by within-group comparisons and superior changes in hip flexion and plantar flexion in the BFRET group. CONCLUSIONS:BFRET is superior to ET alone in enhancing muscle mass and strength in the lower extremities. BFRET may improve the function of the lower extremities through physiological adaptations for muscle hypertrophy. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: ChiCTR2100050206.
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.
Objective To establish an acute low back pain (ALBP) model by simulating low-frequency vibration of helicopters and explore the causes of ALBP in army aviation pilots in order to provide a reliable animal model and evaluation method for its pathogenesis and protection. Methods Forty-eight male SD rats (8 weeks old, weighing 200±20 g) were selected and randomly divided into groups A, B and C, with vibration for 1, 3 and 6 h, respectively, and group D as blank control, with 12 rats in each group. The rats were fixed in sitting posture on a vibrating table (10 Hz, with 6 degree vibration) for corresponding durations during 5 consecutive days. Animal behavioral tests were performed before and on days 1, 4, 7 and 14 after modelling, including paw withdrawal threshold, open field test, rotarod fatigue test, gait analysis, and 24-hour food intake assessment. Finally, light microscopy was used to observe the morphological structure of the multifidus muscle. Results Behavioral examinations revealed that persistent low-frequency vibration resulted in decreased foot-contraction reflex thresholds (P < 0.01), amount of 24-hour food consumption (P < 0.01), count of upright standing (P < 0.05), rotarod velocity at rat falling off (P < 0.05), duty cycle (P < 0.05), footprint surface area (P < 0.05), and walking speed (P < 0.05). Histological observation for the multifidus muscle demonstrated cellular edema and myocyte disorganization accompanied by inflammatory cell infiltration and aggregation. Conclusion Continuous exposure to a low-frequency vibration leads to significant low back pain-related behaviors and histological changes in the lumbar multifidus muscle of rats.
Background and purpose Research to date has lacked definitive evidence to determine whether mirror therapy promotes the recovery of upper extremity function after stroke. Considering that previous studies did not stratify patients based on structural retention, this may be one of the reasons for the negative results obtained in many trials. The goal evaluates the efficacy of TBMT (utilizing an innovatively designed mirror) versus standard occupational therapy for stroke patient's upper limb functionality.Methods and analysis This single-center randomized controlled trial will involve 50 patients with stroke. All patients will be randomly assigned to either the task-based mirror therapy or the control group. The interventions will be performed 5 days per week for 4 weeks. The primary outcomes will be the mean change in scores on both the FMA-UE and modified Barthel Index (MBI) from baseline to 4 weeks intervention and at 12 weeks follow-up between the two groups and within groups. The other outcomes will include the Action Research Arm Test (ARAT), the Nine Hole Peg Test (9HPT), the Functional Independence Measure, and MRI.Discussion This trial will not only to establish that task-based mirror therapy (TBMT) could improve the recovery of hand function after stroke but also to explore the underlying mechanisms. We expect that this finding will clarify the brain activation and brain network mechanisms underlying the improvement of hand function with task-oriented mirror therapy and lead to new ideas for stroke hand function rehabilitation.Trial registration URL: https://www.chictr.org.cn; Unique identifier: ChiCTR2300068855. Registered on March 1, 2023
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.
Spinal cord injury (SCI) results in stalled motor function recovery under the chronic phase. One of the reasons due to the presence of ongoing inflammation. Therefore, regulating the status of immune cells may help reopen the window for neural repair, which represents a potential therapeutic target. In this study, we aimed to investigate whether this could be achieved in mice with cervical 5 crush CSCI (4 W) by utilizing a concentration of 0.5 mg/kg of lipopolysaccharide (LPS) to stimulate microglia/macrophages. Additionally, the mice underwent rehabilitation training for another 6 weeks. Our results showed that systemic injection of LPS enhanced the effects of forelimb rehabilitation training, as evaluated through single pellet grasping (SPG). Electrophysiological studies revealed the restoration of cortical drive to the injured side’s forelimb muscles in the training combined with LPS group. Tract tracing studies demonstrated the reconstruction of cortical innervation to the cervical spinal cord. Furthermore, the levels of pro-inflammatory phenotype markers, such as inducible nitric oxide synthase (INOS) and CD68, decreased, while the expression of anti-inflammatory phenotype markers, including arginase 1 (ARG-1) and CD206, increased. Importantly, this phenotypic switch in microglia/macrophages was accompanied by an increase in phagocytic activity markers as indicated by BODIPY + IBA1 + staining. Collectively, our data suggests that low-dose LPS improves the effects of rehabilitation training by regulating the phenotypic transformation of microglia/macrophages in CSCI. This study provides a fresh perspective and intervention direction for the clinical treatment of chronic spinal cord injuries.
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.
Previous studies reported that the codeletion of PTEN and SOCS3 can greatly enhance the capacity of axon regeneration after central nervous system (CNS) injury. Moreover, the promotion of functional recovery can be improved by rehabilitative training under a use-dependent plasticity mechanism after CNS injury. However, few studies have reported the interaction between these mechanisms after spinal cord injury (SCI). Therefore, we investigated the combined effects of PTEN/SOCS3 coinhibition and rehabilitative training on axon regeneration and upper extremity motor functional improvement after cervical SCI in mice. In this study, we used RNA interference viruses to coinhibit PTEN and SOCS3 and induced a C5 crush injury on the side of preference. The injured upper extremity was trained by single pellet grasping for 4 weeks. We found that the coinjection of viruses significantly increased the expression of p-S6 and p-STAT in the cortex, reduced the dieback pattern of injured axons and promoted traced axon regeneration. More importantly, combination therapy further enhanced axon regeneration compared with PTEN/SOCS3 coinhibition alone. In behavioral tests, the motor performance of the mice in the PTEN/SOCS3 + Training group was better than that of the mice in the other groups. These results indicate that combining task-based rehabilitative training with PTEN/SOCS3 coinhibition further promotes axon regeneration and significant improvement in forelimb skilled motor function after cervical SCI. Our findings provide new therapeutic insights into SCI treatment.
目的:探讨血流限制(blood flow restriction,BFR)联合运动训练对脑卒中患者偏瘫侧下肢功能与步行能力的影响.方法:34例脑卒中患者随机分为BFR联合运动训练组(BRE-ET)(试验组)和运动训练组(ET)(对照组).患者在每日常规康复基础上,试验组接受运动训练和BFR联合运动训练,对照组接受每日2次运动训练.治疗前、治疗中(10天)、治疗后(20天)采用Brunnstrom分期、肌力(MMT)、肌张力(MAS)、主动关节活动度(AROM)、Fugl-Meyer评定量表-下肢部分(FMA-LE)、"起立-行走"计时测试(TUGT)、改良Barthel指数(MBI)对两组患者进行3次评估.结果:治疗20天后,两组偏瘫侧踝跖屈AROM与髋外展肌力与治疗前有明显改善(P<0.001),且试验组明显优于对照组(P=0.014;P=0.048).两组FMA-LE、TUGT、MBI治疗前后均有明显改善(P<0.001).治疗后试验组TUGT与治疗中相比差异有显著性意义(P=0.002).结论:BFR结合运动训练较常规运动训练能更有效的改善脑卒中患者下肢功能,对步行功能、日常生活活动能力有更好临床治疗效果的发展趋势.
人、环境与作业模式(PEO)是在全球范围得到运用的作业实践模式.在PEO模式中,物理治疗师解决患者个人躯体功能障碍,作业治疗师干预日常生活障碍、职业活动参与障碍等,假肢矫形师为患者适配假肢,让患者有重获生活与职业功能的可能.该文对双侧上肢截肢患者应用PEO模式行康复治疗的案例进行了报道,以期为康复工作者提供一定参考.
Spinal cord injury (SCI) is a devastating neurological disorder affecting millions of people worldwide, resulting in severe and permanent disabilities that significantly impact the individual's life. Rehabilitation is a commonly accepted and effective clinical treatment modality for neurological disabilities. A single form of rehabilitation training is, however, limited. Indeed, recent studies have reported that a combination of various training strategies may be more promising in promoting functional recovery. However, few studies have focused on combining different forms of rehabilitative training. Here, we investigated the effect of combining treadmill training and single pellet grasping in a well-established model of murine SCI to assess whether combining rehabilitation approaches improve outcomes. In brief, one week following crush SCI, mice were subjected to the treadmill and single pellet grasping training (SPG) for a period of six weeks. Biotinylated dextran amine (BDA) was used to anterogradely trace corticospinal tract axons to assess functionally relevant axonal sprouting. Our results revealed that the combined training upregulated p-S6 expression, facilitated axonal sprouting, increased the formation of functional synaptic connections, and promoted functional recovery of the upper limb. Our study provides experimental evidence for the benefit of combining multiple modalities of rehabilitative strategies.
Pathological conditions in diabetic feet cause surface temperature variations, which can be captured quantitatively using infrared thermography. Thermal images captured during recovery of diabetic feet after active cooling may reveal richer information than those from passive thermography, but diseased foot regions may exhibit very small temperature differences compared with the surrounding area, complicating plantar foot segmentation in such cold-stressed active thermography. In this study, we investigate new plantar foot segmentation methods for thermal images obtained via cold-stressed active thermography without the complementary information from color or depth channels. To better deal with the temporal variations in thermal image contrast when planar feet are recovering from cold immersion, we propose an image pre-processing method using a two-stage adaptive gamma transform to alleviate the impact of such contrast variations. To improve upon existing deep neural networks for segmenting planar feet from cold-stressed infrared thermograms, a new deep neural network, the Plantar Foot Segmentation Network (PFSNet), is proposed to better extract foot contours. It combines the fundamental U-shaped network structure, a multi-scale feature extraction module, and a convolutional block attention module with a feature fusion network. The PFSNet, in combination with the two-stage adaptive gamma transform, outperforms multiple existing deep neural networks in plantar foot segmentation for single-channel infrared images from cold-stressed infrared thermography, achieving an accuracy of 97.3% and 95.4% as measured by Intersection over Union (IOU) and Dice Similarity Coefficient (DSC) respectively.
Growing evidence has proven the efficacy of physical exercise in remyelination and motor function performance after spinal cord injury (SCI). However, the molecular mechanisms of treadmill training on myelin repair and functional recovery after SCI have not yet been fully studied. Here, we explored the effect of treadmill training on upregulating peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1α)-mediated myelin repair and functional recovery in a mouse model of thoracic T10 contusion injury. A 4-week treadmill training scheme was conducted on mice with SCI. The expression levels of oligodendrogenesis-related protein and PGC1α were detected by immunofluorescence, RNA fluorescence in situ hybridization and western blotting. Transmission electron microscopy (TEM) was used to observe myelin structure. The Basso Mouse Scale (BMS) and CatWalk automated gait analysis system were used for motor function recovery evaluation. Motor evoked potentials (MEPs) were also identified. In addition, adeno-associated virus (AAV)-mediated PGC1α knockdown in OLs was used to further unravel the role of PGC1α in exercise-induced remyelination. We found that treadmill training boosts oligodendrocyte precursor cells (OPCs) proliferation, potentiates oligodendrocytes (OLs) maturation, and increases myelin-related protein and myelin sheath thickness, thus impelling myelin repair and hindlimb functional performance as well as the speed and amplitude of nerve conduction after SCI. Additionally, downregulating PGC1α through AAV attenuated these positive effects of treadmill training. Collectively, our results suggest that treadmill training enhances remyelination and functional recovery by upregulating PGC1α, which should provide a step forward in the understanding of the effects of physical exercise on myelin repair.
This study aims to investigate the effect of insulin-like growth factor 1 (IGF-1) combined with osteopontin (OPN) on the protein expression levels and growth of neuronal axons and its possible mechanism. In this study, IGF-1 combined with OPN promoted neuronal axon growth through the IGF-1R/Akt/mTOR signaling pathway in lipid rafts, and the effect was better than that of either agent alone. This effect was suppressed when given the mTOR inhibitor rapamycin or the lipid raft cholesterol extraction agent methyl-β-cyclodextrin (M-β-CD). Rapamycin could inhibit the expression of phosphorylated ribosomal S6 protein (p-S6) and phosphorylated protein kinase B (p-Akt) and limit axon growth. In addition to the above effects, M-β-CD significantly downregulated the expression of phosphorylated insulin-like growth factor 1 receptor (p-IR). To further investigate the changes in lipid rafts when stimulated by different recombinant proteins, membrane lipid rafts were isolated to observe the changes by western blot. The expression levels of insulin-like growth factor 1 receptor (IR) and P-IR in the IGF-1 combined with OPN group were the highest. When M-β-CD was administered to the lipid rafts of neurons, the enrichment of IR by IGF-1 combined with OPN was weakened, and the p-IR was decreased. Our study found that IGF-1 combined with OPN could promote axon growth by activating the IGF-1R/Akt/mTOR signaling pathway in neuronal lipid rafts.