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Objectives The aim of the study were to (1) investigate what physical and physiological parameters are most important for Frame Running capacity, a parasport for individuals with ambulatory difficulties, and (2) determine whether Frame Running capacity can be predicted in athletes with cerebral palsy. Design Athletes with cerebral palsy (N = 62, Gross Motor Classification System I–V; 2/26/11/21/2) completed a 6-min Frame Running test. Before the 6-min Frame Running test, muscle thickness, passive range of motion (hip, knee, ankle), selective motor control, and spasticity (hip, knee, ankle) were measured in both legs. In total, 54 variables per individual were included. Data were analyzed using correlations, principal component analysis, orthogonal partial least square regression, and variable importance in projection analysis. Results The mean 6-min Frame Running test distance was 789 ± 335 m and decreased with motor function severity. The orthogonal partial least square analysis revealed a modest degree of covariance in the variables analyzed and that the variance in the 6-min Frame Running test distance could be predicted with 75% accuracy based on all the variables measured. Variable importance in projection analysis indicated hip and knee extensor spasticity (negative effect), and muscle thickness (positive effect) arose as the most important factors contributing to Frame Running capacity. Conclusions These results are an important resource to enable optimization of training regimes to improve Frame Running capacity and contribute to evidence-based and fair classification for this parasport., OBJECTIVES: The aim of the study were to (1) investigate what physical and physiological parameters are most important for Frame Running capacity, a parasport for individuals with ambulatory difficulties, and (2) determine whether Frame Running capacity can be predicted in athletes with cerebral palsy. DESIGN: Athletes with cerebral palsy ( N = 62, Gross Motor Classification System I-V; 2/26/11/21/2) completed a 6-min Frame Running test. Before the 6-min Frame Running test, muscle thickness, passive range of motion (hip, knee, ankle), selective motor control, and spasticity (hip, knee, ankle) were measured in both legs. In total, 54 variables per individual were included. Data were analyzed using correlations, principal component analysis, orthogonal partial least square regression, and variable importance in projection analysis. RESULTS: The mean 6-min Frame Running test distance was 789 ± 335 m and decreased with motor function severity. The orthogonal partial least square analysis revealed a modest degree of covariance in the variables analyzed and that the variance in the 6-min Frame Running test distance could be predicted with 75% accuracy based on all the variables measured. Variable importance in projection analysis indicated hip and knee extensor spasticity (negative effect), and muscle thickness (positive effect) arose as the most important factors contributing to Frame Running capacity. CONCLUSIONS: These results are an important resource to enable optimization of training regimes to improve Frame Running capacity and contribute to evidence-based and fair classification for this parasport.

In this study, the properties of circulating extracellular vesicles (EVs) were examined in cerebral palsy (CP) and typically developed (TD) individuals at rest and after aerobic exercise, focusing on the size, concentration, and microRNA cargo of EVs. Nine adult individuals with CP performed a single exercise bout consisting of 45 min of Frame Running, and TD participants completed either 45 min of cycling (n = 10; TD EX) or were enrolled as controls with no exercise (n = 10; TD CON). Blood was drawn before and 30 min after exercise and analyzed for EV concentration, size, and microRNA content. The size of EVs was similar in CP vs. TD, and exercise had no effect. Individuals with CP had an overall lower concentration (similar to 25%, p < 0.05) of EVs. At baseline, let-7a, let-7b and let-7e were downregulated in individuals with CP compared to TD (p < 0.05), while miR-100 expression was higher, and miR-877 and miR-4433 lower in CP compared to TD after exercise (p < 0.05). Interestingly, miR-486 was upregulated similar to 2-fold in the EVs of CP vs. TD both at baseline and after exercise. We then performed an in silico analysis of miR-486 targets and identified the satellite cell stemness factor Pax7 as a target of miR-486. C2C12 myoblasts were cultured with a miR-486 mimetic and RNA-sequencing was performed. Gene enrichment analysis revealed that several genes involved in sarcomerogenesis and extracellular matrix (ECM) were downregulated. Our data suggest that circulating miR-486 transported by EVs is elevated in individuals with CP and that miR-486 alters the transcriptome of myoblasts affecting both ECM- and sarcomerogenesis-related genes, providing a link to the skeletal muscle alterations observed in individuals with CP., Funding Agencies|Futurum-the Academy for Health and Care, Region Jonkoping County, Sweden; Swedish Kidney Foundation [FUTURUM-937508, 870471]; NIH [F2019-0048]; H.K.H. Kronprinsessan Lovisas foerening foer barnasjukvard [P20GM104320-07]; Swedish Society of Medical Research; Sunnerdahls handikappstiftelse; Norrbacka Eugenia Stiftelsen; career grant from the Swedish National Space Agency; [2021-00159]

Synchrotron X-ray computed tomography (SXCT) allows 3D imaging of tissue with a very large field of view and an excellent micron resolution and enables the investigation of muscle fiber atrophy in 3D. The study aimed to explore the 3D micro-architecture of healthy skeletal muscle fibers and muscle fibers at different stages of atrophy (stroke sample = muscle atrophy; spinal cord injury (SCI) sample = severe muscle atrophy). Three muscle samples: a healthy control sample; a stroke sample (atrophic sample), and an SCI sample (severe atrophic sample) were imaged using SXCT, and muscle fiber populations were segmented and quantified for microarchitecture and morphology differences. The volume fraction of muscle fibers was 74.7%, 70.2%, and 35.3% in the healthy, stroke (atrophic), and SCI (severe atrophic) muscle fiber population samples respectively. In the SCI (severe atrophic sample), 3D image analysis revealed fiber splitting and fiber swelling. In the stroke sample (atrophic sample) muscle fiber buckling was observed but was only visible in the 3D analysis. 3D muscle fiber population analysis revealed new insights into the different stages of muscle fiber atrophy not to be observed nor quantified with a 2D histological analysis including fiber buckling, loss of fibers and fiber splitting.

Background: The life expectancy of individuals with intellectual disabilities (ID) is reduced compared to the general population, and one of the main contributors to earlier death is inactivity. Aim: To investigate how 14 weeks of physical activity (PA) in a real-life setting affects cardiovascular fitness, body composition and bone health of adults with ID. Methods: Adults with ID were recruited into a PA-group (N = 52) or a control group (CON, N = 14). The PA-group participated in 14 weeks of PA, and body composition, cardiovascular fitness and bone health were assessed before and after the intervention. Outcomes and Results: Cardiovascular fitness and body composition improved from pre to post within the PA-group: Heart rates (HR) during the last 30 seconds of two increments of a treadmill test, were reduced (3.2 km/h: -4.4 bpm, p<0.05; 4.8 km/h: -7.5 bpm, p<0.001) and fat mass was reduced (-1.02 kg, p<0.05). A between-group difference in favour of the PA-group, were observed in whole body bone mineral density (BMD) (0.024 g/cm2, p<0.05). Conclusions and Implications: Fourteen weeks of PA performed in a real-life setting increased cardiovascular fitness, reduced fat mass and improved BMD in the weight-bearing skeleton in the PA-group. Increased and regular PA seems to be a promising tool to promote physical health in adults with ID.

PURPOSE: To determine the physiological response and association to peak oxygen uptake of the 6-minute Frame Running test (6-MFRT) in persons with cerebral palsy (CP).METHODS: Twenty-four participants with CP, Gross Motor Function Classification System II/III/IV, performed the 6-MFRT. Distance, peak heart rate (HR peak ), peak respiratory exchange ratio (RER peak ), and peak oxygen uptake ( O 2peak ) were measured.RESULTS: HR peak ranged from 146 to 201 beats per minute, RER peak from 0.94 to 1.49, 6-MFRT distance from 179 to 1220 m and O 2peak from 0.62 to 2.18 L/min. HR peak was achieved in 63%, RER peak in 71%. A strong correlation was observed between 6-MFRT and O 2peak .CONCLUSIONS: The 6-MFRT represented a (near) maximum effort for 75% of the participants and the 6-MFRT can be used to estimate oxygen consumption on an individual basis.

Cerebral palsy (CP) is the most common cause of movement disorders in children. Next generation sequencing (NGS) studies have previously shown that expression levels are fundamentally different in children with CP compared to typically developing (TD). However, given that children are in full development, we might expect gene expression levels to change once maturity is reached. Therefore, the main purpose of this study was to investigate gene expression levels of 93 target genes in adults with CP using NGS on muscle biopsies of the gastrocnemius, taken from 22 participants (n = 12 adults with CP; n = 10 TD adults). Subsequently, we carried out NGS of the mitochondrial genome to identify mtDNA variants, and additionally we studied the mitochondrial content using transmission electron microscopy images of the gastrocnemius muscle. Finally, we compared systemic ion levels between TD adults and adults with CP. Differential gene expression levels were found in genes involved in muscle contraction (MYH1 and MYBPC2), mitochondrial function kATP5J, CYCS and NDUFB6), calcium handling (CAMK2B and ATP2A), metabolism (LPL), muscle signaling (MYC, CREB1, ACVR2B, LMNA and TRIM54), and ECM (TNC). There was no statistical significant difference between CP and TD for mtDNA variant frequencies and mitochondrial content. The ion levels of Ca2+, Na+ and K+ were statistically significantly reduced while the Cl− levels were significant increased in adults with CP compared to TD adults. These results highlight that most transcriptional differences are related to muscle function in adults with CP and that mitochondrial function might be altered but not mitochondrial content.

AIM: To provide a detailed gene and protein expression analysis related to mitochondrial biogenesis and assess mitochondrial content in skeletal muscle of children with cerebral palsy (CP). METHOD: Biceps brachii muscle samples were collected from 19 children with CP (mean [SD] age 15y 4mo [2y 6mo], range 9-18y, 16 males, three females) and 10 typically developing comparison children (mean [SD] age 15y [4y], range 7-21y, eight males, two females). Gene expression (quantitative reverse transcription polymerase chain reaction [PCR]), mitochondrial DNA (mtDNA) to genomic DNA ratio (quantitative PCR), and protein abundance (western blotting) were analyzed. Microarray data sets (CP/aging/bed rest) were analyzed with a focused query investigating metabolism- and mitochondria-related gene networks. RESULTS: The mtDNA to genomic DNA ratio was lower in the children with CP compared to the typically developing group (-23%, p=0.002). Out of five investigated complexes in the mitochondrial respiratory chain, we observed lower protein levels of all complexes (I, III, IV, V, -20% to -37%; p<0.05) except complex II. Total peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1 alpha) messenger RNA (p<0.004), isoforms PGC1 alpha 1 (p=0.05), and PGC1 alpha 4 (p<0.001) were reduced in CP. Transcriptional similarities were observed between CP, aging, and 90 days' bed rest. INTERPRETATION: Mitochondrial biogenesis, mtDNA, and oxidative phosphorylation protein content are reduced in CP muscle compared with typically developing muscle. Transcriptional pathways shared between aging and long-term unloading suggests metabolic dysregulation in CP, which may guide therapeutic strategies for combatting CP muscle pathology.

Background: CNS lesions that are acquired early in life e.g. cerebral palsy (CP) disturb muscle development and growth, while CNS injuries acquired later in life e.g. stroke, affect fully matured muscles and cause paresis and atrophy. These differences may result in different contracture phenotypes. Aim: The purpose of this study was to compare systemic biomarkers and gene expression levels in muscle of individuals with CNS lesions acquired early and later in life. Methods: Blood samples and muscle biopsies were analyzed using Enzyme-linked immunosorbent assay and Real-time PCR from n = 24 control participants, n = 14 individuals with cerebral palsy, and n = 12 stroke survivors. Results: Systemic markers: Myostatin was significant-ly decreased in both the cerebral palsy (p = 0.0051), and the stroke group (p = 0.036). Creatine Kinase-MB and C-Reactive Protein were significantly ele-vated in stroke patients only (p < 0.007 & p > 0.034 respectively). Gene ex-pressions: The expression of myostatin (MSTN) was significantly lower in both the ST and the CP group when compared to Ctrl (p = 0.02). In addition, collagen type 4A1 (COL4A1) was significantly lower in the CP group com-pared to the other groups (p = 0.015). Finally, the troponin 1 slow skeletal muscle type was significantly increased in the ST group when compared to both CP and Ctrl (p = 0.03). Conclusion: The downregulation of myostatin in individuals with both early and late CNS injury is likely a compensatory reaction to muscle weakness, reduced muscle mass and/or muscle atrophy. Changes in gene expression may reflect a specific alteration depending on when in life the CNS lesions were acquired. (PDF) Cerebral Palsy and Stroke—Early and Late Brain Lesion Present Differences in Systemic Biomarkers and Gene Expression Related to Muscle Contractures. Available from: https://www.researchgate.net/publication/349557094_Cerebral_Palsy_and_Stroke-Early_and_Late_Brain_Lesion_Present_Differences_in_Systemic_Bio

It is well known that whales in captivity suffer from dorsal fin bending. However, the mechanisms behind this change are poorly understood. Humans can suffer from similar symptoms either after a period of immobilization or after suffering a brain lesion. Therefore, we here speculate whether the bent dorsal fins are reflecting contracture development in whales.

Running is one of the most popular forms of exercise. Even though regular exercise is beneficial to human health, running is also often associated with an increased risk of injury. Lack of shock absorption in running shoes has often been stated as one of the main reasons for why running-related injuries have been on the increase. The aim of the present study was to assess the degree to which ground reaction forces (GRF) can be dissipated in the human leg in a barefoot subject, in connection with diverse physical activities. Acoustic myography (AMG), a non-invasive technique that records pressure waves from contracting muscles as well as the harmonic damping of ligaments, was applied to four anatomical sites on the subject’s leg, during barefoot walking, jogging, running and jumping. The data for walking on a hard surface show much lower ESTiTM parameters than those for the soft surface, and these lower values are observed mainly for sites 1 (toes; 65%) and 2 (ankle; 53%), respectively. AMG parameters for jogging reveal this gait to have very low ESTiTM parameters for site 1 and site 2 (ESTi 2 - 3), yet similar for both surfaces. The data for running on a hard and soft surface revealed much lower ESTiTM parameters (38%) than those for sites 3 (knee) and 4 (hip). The data from the big jump, reveal that on a hard surface, the lowest ESTiTM parameters were for sites 1 (toes; 46%) and 2 (ankle; 27%), compared to values on a soft surface. The speed with which GRFs were transmitted up the leg varied from site to site and also with the type of activity, ranging from undetectable to approx. 60 m/sec. The present study reveals that the ankle joint is exposed to the greatest forces during jumping and running. In addition, this study has confirmed that exercising on a hard surface does indeed increase the stress forces on the toes and ankles. It is interesting to note that the data reveal that toes and ankl

Plastic adaptations are known to take place in muscles, tendons, joints and the nervous system in response to changes in muscle activity. However, few studies have addressed how these plastic adaptations are related. Thus, this study focuses on changes in the mechanical properties of the ankle plantarflexor muscle-tendon unit, stretch reflex activity and spinal neuronal pathways in relation to cast immobilization. The left rat hindlimb from toes to hip was immobilized with a plaster cast for 1, 2, 4 or 8 weeks followed by acute electrophysiological recordings to investigate muscle resistance and stretch reflex torque. Moreover, additional acute experiments were performed after 4 weeks of immobilization to investigate changes in the central gain of the stretch reflex. Monosynaptic reflexes (MSR) were recorded from the L4 and L5 ventral roots following stimulation of the corresponding dorsal roots. Rats developed reduced range of movement in the ankle joint 2 weeks after immobilization. This was accompanied by significant increases in the stiffness of the muscle-tendon complex at 4 and 8 weeks following immobilization. Stretch reflexes were absent in all rats at 4-8 weeks following immobilization. This was associated with increased central gain of the stretch reflex. These data show that numerous inter-related plastic changes occur in muscles, connective tissue and the central nervous system in response to changes in muscle use. The findings provide understanding of coordinated adaptations in multiple tissues and have important implications for prevention and treatment of the negative consequences of immobilization following injuries of the nervous and musculoskeletal systems.

Background: Strenous exercise stimulates the hypothalamic-pituitary (HP) axis in order to ensure homeostasis and promote anabolism. Furthermore, exercise stimulates a transient increase in the neurotrophin brain-derived neurotrophic factor (BDNF) suggested to mediate the anxiolytic effects of exercise. Athletes with secondary functional hypothalamic amenorrhea (FHA) have been reported to have lower BDNF, and a blunted HP axis response to exercise as athletes with overtraining syndrome. Aim: The aim of the study was to investigate the hormonal and BDNF responses to a two-bout maximal exercise protocol with four hours of recovery in between in FHA and eumenorrheic (EUM) athletes. Methods: Eumenorrheic (n = 16) and FHA (n = 14) endurance athletes were recruited from national teams and competitive clubs. Protocols included gynecological examination; body composition (DXA); 7-day assessment of energy availability; blood sampling pre and post the two exercises tests. Results: There were no differences between groups in hormonal responses to the first exercise bout. After the second exercise bout IGFBP-3 increased more in FHA compared with EUM athletes (2.1 +/- 0.5 vs. 0.6 +/- 0.6 mu g/L, p = 0.048). There were non-significant trends toward higher increase in IGF-1 (39.3 +/- 4.3 vs. 28.0 +/- 4.6 mu g/L, p = 0.074), BDNF (96.5 +/- 22.9 vs. 34.4 +/- 23.5 mu g/L, p = 0.058), GH to cortisol ratio (0.329 +/- 0.010 vs. 0.058 +/- 0.010, p = 0.082), and decrease in IGF-1 to IGFBP-3 ratio (-2.04 +/- 1.2 vs. 0.92 +/- 1.22, p = 0.081) in athletes with FHA compared with EUM athletes. Furthermore, there was a non-significant trend toward a higher increase in prolactin to cortisol ratio in EUM athletes compared with athletes with FHA (0.60 +/- 0.15 vs. 0.23 +/- 0.15, p = 0.071). No differences in the hormonal or BDNF responses between the two exercise bouts as a result of menstrual function were found. Conclusion: No major differences in the hormonal or BDNF responses between the two ex

Muscle contractures are a common complication to cerebral palsy (CP). The purpose of this study was to evaluate whether individuals with CP carry specific gene variants of important structural genes that might explain the severity of muscle contractures. Next-generation-sequencing (NGS) of 96 candidate genes associated with muscle structure and metabolism were analyzed in 43 individuals with CP (Gross Motor Function classification system [GMFCS] I, n=10; GMFCS II, n=14; GMFCS III, n=19) and four control participants. In silico analysis of the identified variants was performed. The variants were classified into four categories ranging from likely benign (VUS0) to highly likely functional effect (VUS3). All individuals with CP were classified and grouped according to their GMFCS level: Statistical comparisons were made between GMFCS groups. Kruskal-Wallis tests showed significantly more VUS2 variants in the genes COL4 (GMFCS I-III; 1, 1, 5, respectively [p < .04]), COL5 (GMFCS I-III; 1, 1, 5 [p < .04]), COL6 (GMFCS I-III; 0, 4, 7 [p < .003]), and COL9 (GMFCS I-III; 1, 1, 5 [p < .04]), in individuals with CP within GMFCS Level III when compared to the other GMFCS levels. Furthermore, significantly more VUS3 variants in COL6 (GMFCS I-III; 0, 5, 2 [p < .01]) and COL7 (GMFCS I-III; 0, 3, 0 [p < .04]) were identified in the GMFCS II level when compared to the other GMFCS levels. The present results highlight several candidate gene variants in different collagen types with likely functional effects in individuals with CP.

When aerobic exercise is performed following skilled motor practice, it can enhance motor memory consolidation. Previous studies have suggested that dopamine may play a role in motor memory consolidation, but whether it is involved in the exercise effects on consolidation is unknown. Hence, we aimed to investigate the influence of dopaminergic pathways on the exercise-induced modulation of motor memory consolidation. We compared the effect of acute exercise on motor memory consolidation between the genotypes that are known to affect dopaminergic transmission and learning. By combining cluster analyses and fitting linear models with and without included polymorphisms, we provide preliminary evidence that exercise benefits the carriers of alleles that are associated with low synaptic dopamine content. In line with previous reports, our findings implicate dopamine as a modulator of the exercise-induced effects on motor memory consolidation, and suggest exercise as a potential clinical tool to counteract low endogenous dopamine bioavailability. Further experiments are needed to establish causal relations.

Brain-derived neurotrophic factor (BDNF) is a mediator of exercise and nutrition-induced neural plasticity. In children with cerebral palsy (CP), neuromuscular deficits and mobility impairment have a negative impact on their physical activity level and nutritional status, but whether these children have reduced BDNF concentrations is unknown. Therefore, the aim of the present study was to investigate the plasma BDNF concentration, nutritional status, and physical activity level in children with mild to severe CP. Blood sampling, dietary registration, and questionnaires were completed for children with mild CP (gross motor function classification system (GMFCS) I⁻II, n = 31, age 10.6 ± 0.6 years), severe CP (GMFCS IV⁻V, n = 14, age 10.9 ± 1.1 years) and typically developed (TD) children (n = 22, age 10.9 ± 0.6 years). Children with severe CP had ~40% lower plasma BDNF concentration than TD children (p < 0.05). Furthermore, children with severe CP had lower daily physical activity level than TD children (p < 0.01), and a daily intake of energy, n-3 fatty acids, and dietary fibers that was only ~50% of TD (p > 0.001). Reduced plasma BDNF concentrations were observed in children with severe CP. This may be of significance for optimal neural growth and plasticity. This was observed together with low physical activity levels and a suboptimal intake of energy, n-3 fatty acids, and dietary fibers.