Limb Disuse Research Articles

Comparative Analysis of Muscle Activity and Circulatory Dynamics: A Crossover Study Using Leg Exercise Apparatus and Ergometer.

Background and Objectives: Bedridden patients are at a high risk of venous thromboembolism (VTE). Passive devices such as elastic compression stockings and intermittent pneumatic compression are common. Leg exercise apparatus (LEX) is an active device designed to prevent VTE by effectively contracting the soleus muscle and is therefore expected to be effective in preventing disuse of the lower limbs. However, few studies have been conducted on the kinematic properties of LEX. Therefore, this study aimed to compare the exercise characteristics of LEX with those of an ergometer, which is commonly used as a lower-limb exercise device, and examine its effect on the two domains of muscle activity and circulatory dynamics. Materials and Methods: This study used a crossover design in which each participant performed both exercises to evaluate the exercise characteristics of each device. Fifteen healthy adults performed exercises with LEX and an ergometer (Terasu Erugo, SDG Co., Ltd., Tokyo, Japan) for 5 min each and rested for 10 min after each exercise. Muscle activity was measured using surface electromyography (Clinical DTS, Noraxon, Scottsdale, AZ, USA), and circulatory dynamics were recorded using a non-invasive impedance cardiac output meter (Physioflow Enduro, Manatec Biomedical, Paris, France). The primary outcome was the mean percentage of maximum voluntary contraction (%MVC) of the soleus muscle during exercise. Results: The mean %MVC of the soleus muscle was significantly higher in the LEX group, whereas no significant differences were observed across the periods and sequences. Heart rate, stroke volume, and cardiac output increased during exercise and decreased thereafter; however, the differences between the devices were not significant. Conclusions: LEX may not only have a higher thromboprophylaxis effect, but also a higher effect on preventing muscle atrophy as a lower-extremity exercise device. Additionally, LEX could potentially be used safely in patients who need to be monitored for changes in circulatory dynamics.

Impact of Aging and Disuse on Markers of Endoplasmic Reticulum Stress and the Unfolded Protein Response

Aging and disuse can impair skeletal muscle responses to stimuli and are key drivers in dysregulated proteostasis. Such dysfunction can lead to an accumulation of misfolded proteins resulting in endoplasmic reticulum stress (ERS) and the unfolded protein response (UPR). While the UPR blunts global translation and enhances the production of chaperones and foldases, little is known about ERS responses across the lifespan and in disuse contexts. Therefore, the purposes of this study were to examine if: i) the expression of ERS and UPR effector proteins differ across the lifespan in rats, and ii) age-associated patterns were recapitulated by 10 days of hindlimb casting in a separate cohort of rats. We hypothesized that aging would enhance the expression of ERS related proteins, and this expression pattern would be mimicked by 10 days of limb disuse. Male Fischer 344 rats were sacrificed at 3, 6, 12, 18, and 24 months (mo) of age, and plantaris (PLT) and soleus (SOL) muscles were collected for analysis. Six mo female Wistar rats were sacrificed after either 10 days of hindlimb casting or continued ambulation (age matched control), after which whole gastrocnemius muscles were collected for analysis. The effector eukaryotic initiation factor 2 alpha (eIF2a) was different across the lifespan (phospho/pan) in PLT and SOL muscles (p<0.001) and was upregulated in the PLT at 24 mo as compared to 3 mo (P=0.006). The downstream UPR effector C/EBP homologous protein (CHOP) was differentially expressed across the lifespan in PLT and SOL (p<0.001). CHOP was upregulated ~2.79 and 3.08-fold at 18 and 24 mo respectively in the SOL (p<0.001), and 2.62 and 2.44-fold at 18 and 24 mo respectively in the PLT. Finally, principal effector Activating Transcription Factor 6 (ATF6) was differentially expressed across the lifespan (cleaved/pan) in the PLT and SOL (P≤0.024) whereby a 1.23-fold up-regulation was evident at 18 mo in the SOL (P=0.035) and 1.34-fold at 18 mo in the PLT (P=0.026). The CHOP and ATF6 proteins were similarly dysregulated in our disuse model, whereby 1.83-fold (p<0.001) and 1.30-fold (P=0.002) greater values were observed in hind limb casted versus control rats. Effectors of the UPR pathway are upregulated in skeletal muscle across the lifespan in rats, and this effect is recapitulated with disuse. These findings warrant further research for potential therapeutics related to age- and disuse-related skeletal muscle atrophy. Funding for this study was provided by discretionary laboratory funds from MDR. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

A decision tree algorithm to identify predictors of post-stroke complex regional pain syndrome

This prospective cohort study aimed to identify the risk factors for post-stroke complex regional pain syndrome (CRPS) using a decision tree algorithm while comprehensively assessing upper limb and lower limb disuse and physical inactivity. Upper limb disuse (Fugl-Meyer assessment of upper extremity [FMA-UE], Action Research Arm Test, Motor Activity Log), lower limb disuse (Fugl-Meyer Assessment of lower extremity [FMA-LE]), balance performance (Berg balance scale), and physical inactivity time (International Physical Activity Questionnaire-Short Form [IPAQ-SF]) of 195 stroke patients who visited the Kishiwada Rehabilitation Hospital were assessed at admission. The incidence of post-stroke CRPS was 15.4% in all stroke patients 3 months after admission. The IPAQ, FMA-UE, and FMA-LE were extracted as risk factors for post-stroke CRPS. According to the decision tree algorithm, the incidence of post-stroke CRPS was 1.5% in patients with a short physical inactivity time (IPAQ-SF < 635), while it increased to 84.6% in patients with a long inactivity time (IPAQ-SF ≥ 635) and severe disuse of upper and lower limbs (FMA-UE score < 19.5; FMA-LE score < 16.5). The incidence of post-stroke CRPS may increase with lower-limb disuse and physical inactivity, in addition to upper-limb disuse. Increasing physical activity and addressing lower- and upper-limb motor paralysis may reduce post-stroke CRPS.

Exploring structural brain changes in children with neonatal brachial plexus palsy: a voxel-based morphometry analysis

BACKGROUND: Obstetric brachial plexus palsy (OBPP) is paralysis of the upper limb resulting from nerve injury during vaginal delivery. Although current treatment approaches frequently lead to complete reinnervation of the limb, some patients show long-term motor deficits. These impairments may result from upper limb disuse that causes structural brain changes. AIM: This study aimed to compare deep gray matter volumes between children with OBPP and healthy controls. METHODS: We analyzed the structural magnetic resonance imaging results of 46 children with OBPP (n=24, mean age — 10.20, of whom 12 were girls) and healthy age-matched controls (n=22, mean age — 9.63, of whom 10 were girls) using a voxel-based morphometry technique in SPM12 package (Statistical Parametric Mapping) in MATLAB R2019b. To minimize false discoveries, we used a stringent procedure to control the family-wise error rate. RESULTS: We found volumetric brain differences between children with OBPP and healthy controls (all FWE-corrected p 0.005). Children with OBPP had significantly lower gray matter volumes in the left amygdala, bilateral hippocampus, and right entorhinal cortex. CONCLUSION: Integrating our findings with previous work, we speculate that the amygdala–hippocampus–entorhinal cortex complex might play a significant role in motor disorders.

Assessment of the Interval to Diagnosis in Pediatric Bone Sarcoma.

The timely diagnosis of primary bone malignancies in pediatric patients is critical to clinical outcomes. The purpose of this study is to investigate the initial presentation of pediatric bone sarcoma patients to an academic health care system and assess the current interval to diagnosis. We conducted a retrospective review of pediatric patients (aged 1-18) with biopsy-proven diagnosis of osteosarcoma or Ewing sarcoma presenting between 2004 and 2020. All living patients had 1 year or more of follow-up. Primary outcomes were interval to diagnosis, clinical features on initial presentation, percent of patients with negative radiographic workup at initial presentation, and number of health care encounters before diagnosis. Seventy-one patients (osteosarcoma, 51; Ewing sarcoma, 20) were included. Average age at presentation was 13.1 ± 3.3 years (range, 4.4-18.3). Average symptom duration was 5.4 ± 13.9 months (range, 0.1-84). Clinical features at initial presentation included limb/back pain (91.5% of patients), activity modification/pain medication use (78.9%), palpable mass (40.8%), night pain (35.2%), limp (25.4%), limb disuse (18.3%), and recent fever history (2.8%). Fourteen of 71 patients (19.7%) had negative radiographs at initial presentation. Average number of health care encounters before diagnosis was 1.9 ± 0.6 (range, 1.0-4.0), with most in the outpatient pediatrician clinics (81.2%) and emergency department (18.3%). Average time to diagnosis from initial presentation was 19.5 ± 65 days (range, 0-493); the 14 patients with initial negative radiographs had a statistically significant prolonged interval to diagnosis of 54 ± 134 days (range, 0-493; P = 0.018). We found pediatric patients with primary bone sarcoma present with an average interval to diagnosis of 20 days. Twenty percent of patients had a significantly prolonged interval to diagnosis of 54 days. Clinical features suggest night pain is not a sensitive indicator. In patients of appropriate age with persistent unilateral pain in suspicious locations, early advanced imaging with magnetic resonance imaging should be considered.

Chronic stroke survivors' perspective on the use of serious games to motivate upper limb rehabilitation - a qualitative study.

Upper limb paresis occurs quite commonly after stroke and may result in the affected limb's disuse or learned non-use. As a result, its cortical representation may be suppressed, further inhibiting its spontaneous utilization, resulting in motor function deterioration, increase in spasticity, joint stiffness and pain.The aim of this work was to involve stroke survivors in a qualitative study within a user centred design process to better understand the perspectives of stroke survivors on virtual reality - based serious games (SG) for upper limb rehabilitation during the chronic phase and use those insights to design a VR-based serious games which promotes activation of the affected cortical area.A qualitative research method was performed using a multi professional focus group discussion, including a representative group of stroke survivors.With the insights of this work, the authors initiated the design of a VR-based SG prototype for upper limb rehabilitation with two modes, one version to be played with any arm to pick a virtual hammer and hit targeted objects, and other version, a mirror version based on mirror therapy.

Resolving trabecular metaphyseal bone profiles downstream of the growth plate adds value to bone histomorphometry in mouse models.

Histomorphometry of rodent metaphyseal trabecular bone, by histology or microCT, is generally restricted to the mature secondary spongiosa, excluding the primary spongiosa nearest the growth plate by imposing an 'offset'. This analyses the bulk static properties of a defined segment of secondary spongiosa, usually regardless of proximity to the growth plate. Here we assess the value of trabecular morphometry that is spatially resolved according to the distance 'downstream' of-and thus time since formation at-the growth plate. Pursuant to this, we also investigate the validity of including mixed primary-secondary spongiosal trabecular bone, extending the analysed volume 'upstream' by reducing the offset. Both the addition of spatiotemporal resolution and the extension of the analysed volume have potential to enhance the sensitivity of detection of trabecular changes and to resolve changes occurring at different times and locations. Two experimental mouse studies of trabecular bone are used as examples of different factors influencing metaphyseal trabecular bone: (1) ovariectomy (OVX) and pharmacological prevention of osteopenia and (2) limb disuse induced by sciatic neurectomy (SN). In a third study into offset rescaling, we also examine the relationship between age, tibia length, and primary spongiosal thickness. Bone changes induced by either OVX or SN that were early or weak and marginal were more pronounced in the mixed primary-secondary upstream spongiosal region than in the downstream secondary spongiosa. A spatially resolved evaluation of the entire trabecular region found that significant differences between experimental and control bones remained undiminished either right up to or to within 100 μm from the growth plate. Intriguingly, our data revealed a remarkably linear downstream profile for fractal dimension in trabecular bone, arguing for an underlying homogeneity of the (re)modelling process throughout the entire metaphysis and against strict anatomical categorization into primary and secondary spongiosal regions. Finally, we find that a correlation between tibia length and primary spongiosal depth is well conserved except in very early and late life. These data indicate that the spatially resolved analysis of metaphyseal trabecular bone at different distances from the growth plate and/or times since formation adds a valuable dimension to histomorphometric analysis. They also question any rationale for rejecting primary spongiosal bone, in principle, from metaphyseal trabecular morphometry.

Changes in postural sway during upright stance after short-term lower limb physical inactivity: A prospective study.

Previous studies have reported that motor behavior is affected by short-term physical inactivity using cast immobilization; however, the effects of inactivity on postural sway are not well-understood. This study aimed to investigate the effects of short-term lower limb disuse on postural sway in the upright position after cast removal. Twenty-two healthy young adults were enrolled, and each participant’s lower limb on one side was fixed with a soft bandage and medical splint made from metal and soft urethane for 10 h. Fluctuations in the center of pressure (COP) were measured before and after immobilization; the total trajectory length, mean velocity, COP root mean square (RMS) area, mean medial-lateral (M-L) COP, and mean anterior-posterior (A-P) COP were selected as evaluation parameters. Compared with the postural sway before cast application, we noted an increase and shift (from the fixed to the nonfixed side) in the postural sway after cast removal. Our results therefore suggest that short-term disuse may cause acute changes in COP movements during quiet standing. Moreover, patients may maintain their standing posture by adopting a compensatory strategy involving lateral control, similar to individuals with stroke and patients who have undergone total knee arthroplasty.

Anti-sclerostin antibodies and abaloparatide have additive effects when used as a countermeasure against disuse osteopenia in female rats.

Prolonged disuse and substantial mechanical unloading are particularly damaging to skeletal integrity. Preclinical studies in rodents and clinical studies have highlighted the need for potent bone anabolic drugs to counteract disuse-induced osteopenia. The aim of present study was to compare the efficacy of romosozumab (Scl-Ab) and abaloparatide (ABL), alone or in combination, to prevent botulinum toxin (BTX) induced bone loss in a rat model. Eighty female Wistar rats were divided into the following six groups: 1. Baseline (n=12); 2. Control (Ctrl) (n=12); 3. BTX (n=12); 4. BTX+Scl-Ab (n=16); 5. BTX+ABL (n=12); and 6. BTX+Scl-Ab + ABL (n=16). Disuse was achieved by injecting 4IU BTX into the hind limb musculature at study start. Scl-Ab (25mg/kg) was injected s.c. twice weekly, while ABL (80μg/kg) was injected s.c. five days a week for four weeks. Hind limb disuse dramatically decreased muscle mass and skeletal integrity and deteriorated the cortical morphology and trabecular microstructure. Treatment with Scl-Ab alone prevented most of the adverse cortical and trabecular effects of disuse, while ABL monotherapy mainly attenuated the disuse-induced loss of femoral areal bone mineral density (aBMD). Moreover, the combination of Scl-Ab and ABL not only counteracted most of the negative skeletal effects of unloading, but also increased aBMD (+10% and +20%), epiphyseal trabecular bone volume fraction (BV/TV) (+25% and +73%), and metaphyseal bone strength (+18% and +30%) significantly above that of Scl-Ab or ABL monotherapy, respectively. The potent and additive osteoanabolic effect of Scl-Ab and ABL, when given in combination, is highly intriguing and underlines that an osteoanabolic bone gain can be maximized by utilizing two pharmaceuticals targeting different cellular signaling pathways. From a clinical perspective, a combination treatment may be warranted in patients where the osteoanabolic effect of either monotherapy is not sufficient, or if a dose-reduction is required due to adverse effects.

Targeting Endogenous Antioxidant Capacity to Prevent Vascular Dysfunction Induced by Limb Immobilization

BackgroundBrief periods of limb disuse that accompany orthopedic injuries can impair vascular function and increase cardiovascular disease risk. Specifically, limb immobilization elicits a decrease in vascular shear stress which leads to an increase in oxidative stress and impaired vasodilation. We hypothesized that increasing the activation of nuclear factor‐erythroid factor 2‐related factor 2 (Nrf2), a critical transcription factor that regulates expression of endogenous antioxidants, using a novel, naturally occurring, supplement (PB125), would preserve vascular function during 14 days of limb immobilization.MethodsTen young, healthy individuals were randomized to receive either PB125 (100mg, N=6, 3M/3F, 28±5 y, BMI= 25±6 kg/m2) or placebo (N=4, 1M/3F, 23±4 y, BMI=24±3 kg/m2). Utilizing Doppler ultrasound, before and after 14 days of leg immobilization, leg blood flow (LBF) and vascular conductance (LVC) were measured in the common femoral artery at rest and during passive leg movement (PLM), and during knee‐extensor (KE) exercise at 3 relative intensities (40, 60, 80% of max; KE max = 35±10W). Additionally, flow mediated dilation (FMD) and post‐occlusive reactive hyperemia were assessed in the popliteal and brachial arteries.ResultsLower limb immobilization reduced daily step count by 53 ± 19% in both groups (PB125 vs. placebo p &gt; 0.05). Femoral, popliteal, and brachial artery diameters were not significantly different following immobilization. Resting LBF and LVC were lower following immobilization in the placebo group (pre vs. post; LBF: 485±124 vs. 357±106 ml/min, p = 0.001; LVC: 5.2±1.1 vs. 3.7±0.9 ml/min/mmHg, p = 0.001), but were preserved in the PB125 group (LBF: 239±63 vs. 237±78 ml/min, p &gt; 0.05; LVC: 2.6±0.6 vs. 2.6±0.7 ml/min/mmHg, p &gt; 0.05). However, LBF and LVC during KE exercise were not impacted by limb immobilization. Microvascular function, as assessed by the hyperemic response to PLM, was diminished in the placebo group (LVC Δpeak: 6.8±2.8 vs. 3.7±1.4 ml/min/mmHg, p = 0.049), but preserved in the PB125 group (LVC Δpeak: 3.0±0.6 vs. 3.0±1.8 ml/min/mmHg p &gt; 0.05). Conversely, microvascular function, assessed by reactive hyperemia, was unchanged in both the popliteal and brachial arteries. Macrovascular function changes due to immobilization were limb‐specific, with a decrease in popliteal artery FMD with placebo (6.5±4.1 vs. 1.9±1.6 %, p = 0.046) and preservation with PB125 (4.4±3.6 vs. 2.8±1.9 %, p &gt; 0.05), while brachial artery FMD was unchanged in both groups (p &gt; 0.05).ConclusionsLimb immobilization induced both microvascular and macrovascular changes in the leg which may contribute to the attenuated LBF and LVC at rest. Administration of PB125 preserved vascular function during disuse, presumably by mitigating the deleterious impact of oxidative stress. Hence, PB125 supplementation, and, therefore, augmented endogenous antioxidant capacity, appears to mitigate the negative vascular effects of limb disuse.

Primary bone retention in a young adult male with limb disuse: a bioarchaeological case study

ABSTRACT Bone mineral and mass are low in limb bones that experience prolonged lack of, or minimal, mechanical stimulation. Cases of ancient human limb paralysis offering an opportunity to examine histological markers of cortical bone modelling and remodelling are rare. To improve our understanding of the spectrum of bone tissue response to its muscular disuse environment in archaeological contexts, we tested whether bone histology in an individual afflicted with long-term loss of muscle function showed unremodelled primary bone due to minimal/absent, mechanical stimulation. We examined cortical bone histology in a 1906–1523 cal BC atrophied post-cranium of a young adult (mid-20s) male who had suffered from Klippel-Feil Syndrome Type III, experiencing minimally paraplegia and potentially complete or intermittent quadriplegia in late childhood/early adolescence. Samples taken from the humeral and femoral midshaft displayed thin cortices and extensive retention of primary bone with only localised Haversian tissue or isolated secondary osteons. The retention of widespread primary bone and thin cortices in this adult individual is evidence for stunted modelling and remodelling due to immobility during early ontogeny. Our bone histology descriptions should be of interest to palaeobiologists investigating the effects of physical inactivity on bone microstructure in fossilised and archaeological human remains.

Passive muscle heating attenuates the decline in vascular function caused by limb disuse.

Limb disuse has profound negative consequences on both vascular and skeletal muscle health. The purpose of this investigation was to determine whether repeated application of passive heat, applied to the knee extensor muscles, could mitigate the detrimental effects of limb disuse on vascular function. This was a randomized, single-blinded placebo controlled trial. Twenty-one healthy volunteers (10 women, 11 men) underwent 10days of unilateral lower limb immobilization and were randomized to receive either a daily 2h sham (Imm) or heat treatment (Imm+H) using pulsed shortwave diathermy. Vascular function was assessed with Doppler ultrasound of the femoral artery and the passive leg movement technique. Biopsies of the vastus lateralis were also collected before and after the intervention. In Imm, femoral artery diameter (FAD) and PLM-induced hyperaemia (HYP) were reduced by 7.3% and 34.3%, respectively. Changes in both FAD (4% decrease; P=0.0006) and HYP (7.8% increase; P=0.003) were significantly attenuated in Imm+H. Vastus lateralis capillary density was not altered in either group. Immobilization significantly decreased expression of vascular endothelial growth factor (P=0.006) and Akt (P=0.001), and increased expression of angiopoietin 2 (P=0.0004) over time, with no differences found between groups. Immobilization also upregulated elements associated with remodelling of the extracellular matrix, including matrix metalloproteinase 2 (P=0.0046) and fibronectin (P=0.0163), with no differences found between groups. In conclusion, limb immobilization impairs vascular endothelial function, but daily muscle heating via diathermy is sufficient to counteract this adverse effect. These are the first data to indicate that passive muscle heating mitigates disuse-induced vascular dysfunction. KEY POINTS: Limb disuse can be unavoidable for many of reasons (i.e. injury, bed rest, post-surgery), and can have significant adverse consequences for muscular and vascular health. We tested the hypothesis that declines in vascular function that result from lower limb immobilization could be mitigated by application of passive heat therapy. This report shows that 10days of limb immobilization significantly decreases resistance artery diameter and vascular function, and that application of passive heat to the knee extensor muscle group each day for 2h per day is sufficient to attenuate these declines. Additionally, muscle biopsy analyses showed that 10days of heat therapy does not alter capillary density of the muscle, but upregulates multiple factors indicative of a vascular remodelling response. Our data demonstrate the utility of passive heat as a therapeutic tool to mitigate losses in lower limb vascular function that occur from disuse.

Motor imagery practice benefits during arm immobilization

Motor imagery (MI) is known to engage motor networks and is increasingly used as a relevant strategy in functional rehabilitation following immobilization, whereas its effects when applied during immobilization remain underexplored. Here, we hypothesized that MI practice during 11 h of arm-immobilization prevents immobilization-related changes at the sensorimotor and cortical representations of hand, as well as on sleep features. Fourteen participants were tested after a normal day (without immobilization), followed by two 11-h periods of immobilization, either with concomitant MI treatment or control tasks, one week apart. At the end of each condition, participants were tested on a hand laterality judgment task, then underwent transcranial magnetic stimulation to measure cortical excitability of the primary motor cortices (M1), followed by a night of sleep during which polysomnography data was recorded. We show that MI treatment applied during arm immobilization had beneficial effects on (1) the sensorimotor representation of hands, (2) the cortical excitability over M1 contralateral to arm-immobilization, and (3) sleep spindles over both M1s during the post-immobilization night. Furthermore, (4) the time spent in REM sleep was significantly longer, following the MI treatment. Altogether, these results support that implementing MI during immobilization may limit deleterious effects of limb disuse, at several levels of sensorimotor functioning.

Daily protein supplementation attenuates immobilization-induced blunting of postabsorptive muscle mTORC1 activation in middle-aged men.

Disuse-induced muscle atrophy is accompanied by a blunted postprandial response of the mammalian target of rapamycin complex 1 (mTORC1) pathway. Conflicting observations exist as to whether postabsorptive mTORC1 pathway activation is also blunted by disuse and plays a role in atrophy. It is unknown whether changes in habitual protein intake alter mTORC1 regulatory proteins and how they may contribute to the development of anabolic resistance. The primary objective of this study was to characterize the downstream responsiveness of skeletal muscle mTORC1 activation and its upstream regulatory factors, following 14 days of lower limb disuse in middle-aged men (45-60 yr). The participants were further randomized to receive daily supplementation of 20 g/d of protein (n = 12; milk protein concentrate) or isocaloric carbohydrate placebo (n = 13). Immobilization reduced postabsorptive skeletal muscle phosphorylation of the mTORC1 downstream targets, 4E-BP1, P70S6K, and ribosomal protein S6 (RPS6), with phosphorylation of the latter two decreasing to a greater extent in the placebo, compared with the protein supplementation groups (37% ± 13% vs. 14% ± 11% and 38% ± 20% vs. 25% ± 8%, respectively). Sestrin2 protein was also downregulated following immobilization irrespective of supplement group, despite a corresponding increase in its mRNA content. This decrease in Sestrin2 protein was negatively correlated with the immobilization-induced change in the in silico-predicted regulator miR-23b-3p. No other measured upstream proteins were altered by immobilization or supplementation. Immobilization downregulated postabsorptive mTORC1 pathway activation, and 20 g/day of protein supplementation attenuated the decrease in phosphorylation of targets regulating muscle protein synthesis.

Spinal cord injury and vascular function: evidence from diameter-matched vessels.

The effect of a spinal cord injury (SCI) on vascular function has been clouded by both the physiological and mathematical bias of assessing vasodilation in arteries with differing diameters both above and below the lesion and when comparing with healthy, nondisabled controls (CTRL). Thus, we measured vascular function, with flow-mediated vasodilation (FMD), in 10 SCI and 10 CTRL with all arteries matched for diameter (≈0.5 cm): brachial artery (BA, arm, functional limb in both groups) and popliteal artery (PA, leg, disused limb in SCI, functional limb in CTRL). PA %FMD was significantly attenuated in SCI (5.6 ± 0.6%) compared with CTRL (8.4 ± 1.3%), with no difference in the BA (SCI: 8.6 ± 0.9%; CTRL: 8.7 ± 0.7%). However, unlike the arm, where muscle mass was preserved, the legs of the SCI were significantly smaller than CTRL (∼70%). Thus, reactive hyperemia (RH), which is heavily dependent on the volume of muscle occluded, in the PA was attenuated in the SCI (144 ± 22 mL) compared with CTRL (258 ± 16 mL) but not different in the BA. Consequently, shear rate was significantly diminished in the PA of the SCI, such that %FMD/shear rate (vascular responsiveness) was actually greater in the SCI (1.5 ± 0.1% · s-1) than CTRL (1.2 ± 0.1% · s-1). Of note, this was significantly greater than both their own BA (0.9 ± 0.1% · s-1) and that of the CTRL (0.9 ± 0.1% · s-1). Therefore, examining vessels of similar size, this study reveals normal vascular function above the lesion and vascular dysfunction below the lesion. However, below the lesion there was, actually, evidence of increased vascular responsiveness in this population.NEW & NOTEWORTHY This study examined the effect of a spinal cord injury (SCI) and subsequent limb disuse on vascular function, assessed by %FMD, in diameter-matched vessels above and below the lesion in subjects with SCI and controls. The results reveal normal vascular function above the lesion and vascular dysfunction below the lesion (%FMD). However, below the lesion there was, actually, evidence of increased vascular responsiveness (%FMD/shear rate) in this population.

Blood Flow Restriction Combined with Electrical Stimulation Attenuates Thigh Muscle Disuse Atrophy.

This study aimed to investigate the effects of blood flow restriction (BFR) combined with electrical muscle stimulation (EMS) on skeletal muscle mass and strength during a period of limb disuse. Thirty healthy participants (22 ± 3 yr; 23 ± 3 kg·m-2) were randomly assigned to control (CON; n = 10), BFR alone (BFR; n = 10), or BFR combined with EMS (BFR + EMS; n = 10). All participants completed unloading of a single leg for 14 d, with no treatment (CON), or while treated with either BFR or BFR + EMS (twice daily, 5 d·wk-1). BFR treatment involved arterial three cycles of 5-min occlusion using suprasystolic pressure, each separated by 5 min of reperfusion. EMS (6 s on, 15 s off; 200 μs; 60 Hz; 15% maximal voluntary contraction [MVC]) was applied continuously throughout the three BFR cycles. Quadriceps muscle mass (whole-thigh lean mass via dual-energy x-ray absorptiometry and vastus lateralis [VL] muscle thickness via ultrasound) and strength (via knee extension MVC) were assessed before and after the 14-d unloading period. After limb unloading, whole-thigh lean mass decreased in the control group (-4% ± 1%, P < 0.001) and BFR group (-3% ± 2%, P = 0.001), but not in the BFR + EMS group (-0.3% ± 3%, P = 0.8). VL muscle thickness decreased in the control group (-4% ± 4%, P = 0.005) and was trending toward a decrease in the BFR group (-8% ± 11%, P = 0.07) and increase in the BFR + EMS group (+5% ± 10%, P = 0.07). Knee extension MVC decreased over time (P < 0.005) in the control group (-18% ± 15%), BFR group (-10% ± 13%), and BFR + EMS group (-18% ± 15%), with no difference between groups (P > 0.5). Unlike BFR performed in isolation, BFR + EMS represents an effective interventional strategy to attenuate the loss of muscle mass during limb disuse, but it does not demonstrate preservation of strength.

Motor Imagery Training During Arm Immobilization Prevents Corticomotor Idling: An EEG Resting-State Analysis.

Limb disuse causes overt, measurable alterations in motor functions. Motor imagery (MI) practice has been used as a behavioral strategy to prevent motor impairments due to limb disuse or immobilization. Yet, how MI operates at the neural level in the context of short-term limb immobilization remains understudied. We hypothesized that MI treatment applied during 12h of arm immobilization prevents immobilization-related changes in resting-state electroencephalographic (rsEEG) power and functional connectivity. Fourteen participants first underwent rsEEG after 12h of normal motor activity (without immobilization). Then, rsEEG recording was performed after 12h of arm immobilization either with MI treatment or without, each conditionseparated by 1week, according to a randomized within-subjects design. MI treatment consisted in performing varied visual and kinaesthetic MI exercises (5 sessions of 15min every two hours). The results showed that in the delta, theta, alpha and beta frequency bands, interhemispheric difference in sensors power over the motor cortex (i.e. C3 vs. C4) was reduced after arm immobilization, while it did not change when MI treatment was delivered during the immobilization period. Moreover, functional connectivity across the sensors-network in the delta (1-4Hz) and alpha (8-12Hz) frequency bands decreased after immobilization while it was restored by MI treatment. To conclude, MI counteracts functional neural changes within and between motor regions in the context of limb immobilization. Practical applications for motor rehabilitation strategies, particularly in stroke patients, are also discussed.

Rodent model of disuse-induced bone loss by hind limb injection with botulinum toxin A

Bone loss materializes rapidly after immobilization or mechanical unloading. Hind limb injection with botulinum toxin A (BTX) is a highly reproducible animal model for disuse-induced bone loss. Here we describe an easy-to-use and enhanced version of the method employing multiple hind limb injections with BTX to induce a pervasive muscle paralysis and thereby disuse of the hind limb. Thirty-six 12–14-week-old female Wistar rats were stratified into three groups: Baseline (Base), Control (Ctrl), and BTX. Disuse was achieved by injecting BTX directly into the right quadriceps femoris muscle, the hamstring muscles, and the posterior calf muscles. The rats were sacrificed after six weeks, and the right rectus femoris muscle and femur were isolated and analyzed. Hind limb disuse resulted in a significant and substantial loss of both muscle mass and bone mass. The loss of bone mass was accompanied by a reduction of trabecular bone mass and a deterioration of the trabecular micro-architecture with a reduction of trabecular thickness and trabecular number compared to Ctrl. In addition, the trabeculae changed from a more plate-like towards a more rod-like shape as indicated by an increase in the structure model index.•Multiple injections with BTX targeting muscles on both the anterior and posterior thigh and the calf ensure a uniform and pervasive muscle paralysis and hind limb disuse.•Hind limb injections with BTX results in a substantial loss of muscle and bone mass and deterioration of the trabecular micro-architecture.•The induction of hind limb disuse with BTX is highly reproducible.

Determining User Intent of Partly Dynamic Shoulder Tasks in Individuals With Chronic Stroke Using Pattern Recognition.

Stroke remains the leading cause of long-term disability in the US. Although therapy can achieve limited improvement of paretic arm use and performance, weakness and abnormal muscle synergies-which cause unintentional elbow, wrist, and finger flexion during shoulder abduction-contribute significantly to limb disuse and compound rehabilitation efforts. Emerging wearable exoskeleton technology could provide powered abduction support for the paretic arm, but requires a clinically feasible, robust control scheme capable of differentiating multiple shoulder degrees-of-freedom. This study examines whether pattern recognition of sensor data can accurately identify user intent for 9 combinations of 1- and 2- degree-of-freedom shoulder tasks. Participants with stroke (n = 12) used their paretic and non-paretic arms, and healthy controls (n = 12) used their dominant arm to complete tasks on a lab-based robot involving combinations of abduction, adduction, and internal and external rotation of the shoulder. We examined the effect of arm (paretic, non-paretic), load level (25% vs 50% maximal voluntary torque), and dataset (electromyography, load cell, or combined) on classifier performance. Results suggest that paretic arm, lower load levels, and using load cell or EMG data alone reduced classifier accuracy. However, this method still shows promise. Further work will examine classifier-user interaction during active control of a robotic device and optimization/minimization of sensors.

Noninvasive Mechanical Joint Loading as an Alternative Model for Osteoarthritic Pain.

ObjectiveMechanisms responsible for osteoarthritic (OA) pain remain poorly understood, and current analgesic therapies are often insufficient. This study was undertaken to characterize and pharmacologically test the pain phenotype of a noninvasive mechanical joint loading model of OA, thus providing an alternative murine model for OA pain.MethodsThe right knees of 12‐week‐old male C57BL/6 mice were loaded at 9N or 11N (40 cycles, 3 times per week for 2 weeks). Behavioral measurements of limb disuse and mechanical and thermal hypersensitivity were acquired before mechanical joint loading and monitored for 6 weeks postloading. The severity of articular cartilage lesions was determined postmortem with the Osteoarthritis Research Society International scoring system. To assess efficacy of various treatments for pain, 9N‐loaded mice were treated for 4 weeks with diclofenac (10 mg/kg), gabapentin (100 mg/kg), or anti–nerve growth factor (anti‐NGF) (3 mg/kg).ResultsMechanical hypersensitivity and weight bearing worsened significantly in 9N‐loaded mice (n = 8) and 11N‐loaded mice (n = 8) 2 weeks postloading, compared to baseline values and nonloaded controls. Maximum OA scores of ipsilateral knees confirmed increased cartilage lesions in 9N‐loaded mice (mean ± SEM 2.8 ± 0.2; P < 0.001) and 11N‐loaded mice (5.3 ± 0.3; P < 0.001), compared to nonloaded controls (1.0 ± 0.0). Gabapentin and diclofenac restored pain behaviors to baseline values after 2 weeks of daily treatment, and gabapentin was more effective than diclofenac. A single injection of anti‐NGF alleviated nociception 2 days after treatment and remained effective for 2 weeks, with a second dose inducing stronger and more prolonged analgesia.ConclusionOur findings show that mechanical joint loading induces OA lesions in mice and a robust pain phenotype that can be reversed using analgesics known to alleviate OA pain in patients. This establishes the use of mechanical joint loading as an alternative model for the study of OA pain.