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Aim: The aim of this observational study was to determine the immune status and function in young adults with cerebral palsy (CP) in comparison to typically developing individuals., Method: Blood samples from 12 individuals with CP (five males, seven females; mean age: 25 years 1 month (5 years 9 months); age range: 19-38 years) and 17 typically developing individuals (eight males, nine females; mean age: 31 years 4 months (6 years 2 months); age range: 20-40 years) were collected before, immediately after, and 1 hour after 45 minutes of frame running or running respectively. Independent t-tests were used to compare heart rate, level of exertion, and baseline cell proportions between groups. Mixed model analysis of variance was utilized to investigate immune cell responses to exercise across groups., Results: Baseline levels of gamma delta (TCRγδ+) T-cells were significantly higher (absolute percentage: +2.65, p = 0.028) in the individuals with CP. Several cell populations showed similar significant changes after exercise in both CP and typically developing groups. Cytotoxic (CD8+) T-cells were only significantly elevated immediately after exercise in the typically developing participants (p < 0.01). Individuals with CP exhibited significantly lower heart rates (-11.1%, p < 0.01), despite similar ratings of perceived exertion., Interpretation: Elevated baseline TCRγδ+ T-cells may indicate low-grade inflammation in adults with CP. Although most of the cell populations showed typical responses to endurance exercise, the absence of response in CD8+ T-cells in individuals with CP may indicate the need for higher intensity during exercise., What This Paper Adds: TCRγδ+ T-cell baseline levels are elevated in adults with cerebral palsy (CP). The CD8+ T-cell response to exercise was blunted in adults with CP. Exercise intensity is decisive for CD8+ T-cell responses in individuals with CP., (© 2023 The Authors. Developmental Medicine & Child Neurology published by John Wiley & Sons Ltd on behalf of Mac Keith Press.)

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., Competing Interests: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

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., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Academy of Pediatric Physical Therapy of the American Physical Therapy Association.)

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 (PGC1α) messenger RNA (p<0.004), isoforms PGC1α1 (p=0.05), and PGC1α4 (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. What this paper adds Cerebral palsy (CP) muscle contains fewer energy-generating organelles than typically developing muscle. Gene expression in CP muscle is similar to aging and long-term bed rest., (© 2021 The Authors. Developmental Medicine & Child Neurology published by John Wiley & Sons Ltd on behalf of Mac Keith Press.)

Introduction: The development of efficient resistance exercise protocols to counteract muscle dysfunction in cerebral palsy is warranted. Whether individuals with cerebral palsy are able to perform iso-inertial resistance (flywheel) exercise in a comparable manner to typically developed subjects has never been experimentally tested., Design: A comparative, controlled study., Subjects: Eight young ambulatory adults with cerebral palsy (mean age 19 years; Gross Motor Function Classification System (GMFCS) I-III) and 8 typically developed control subjects (mean age 21 years)., Methods: Subjects performed acute bouts on the weight-stack and flywheel leg-press device, respectively. Range of motion, electromyography, power, work and muscle thickness (ultrasound) data were collected., Results: Subjects with cerebral palsy were able to produce a greater eccentric/concentric peak power ratio on the flywheel (p < 0.05 vs ratio in weight-stack), however absolute values were lower (p < 0.05 vs weight-stack). Typically developed subjects produced more power per mm of thigh muscle than the cerebral palsy group, independent of leg, device and action., Discussion: Subjects with cerebral palsy could not elicit the eccentric overload seen in typically developed subjects. Furthermore, peak power production per mm muscle was markedly reduced in both legs in subjects with cerebral palsy. In conclusion, this comparative study of weight-stack and flywheel exercise does not support the implementation of the current iso-inertial protocol for young adults with cerebral palsy.

Background: Individuals with cerebral palsy (CP) are less physically active, spend more time sedentary and have lower cardiorespiratory endurance as compared to typically developed individuals. RaceRunning enables high-intensity exercise in individuals with CP with limited or no walking ability, using a three-wheeled running bike with a saddle and a chest plate for support, but no pedals. Training adaptations using this type of exercise are unknown., Methods: Fifteen adolescents/young adults (mean age 16, range 9-29, 7 females/8 males) with CP completed 12 weeks, two sessions/week, of RaceRunning training. Measurements of cardiorespiratory endurance (6-min RaceRunning test (6-MRT), average and maximum heart rate, rate of perceived exertion using the Borg scale (Borg-RPE)), skeletal muscle thickness (ultrasound) of the thigh (vastus lateralis and intermedius muscles) and lower leg (medial gastrocnemius muscle) and passive range of motion (pROM) of hip, knee and ankle were collected before and after the training period., Results: Cardiorespiratory endurance increased on average 34% (6-MRT distance; pre 576 ± 320 m vs. post 723 ± 368 m, p < 0.001). Average and maximum heart rate and Borg-RPE during the 6-MRT did not differ pre vs. post training. Thickness of the medial gastrocnemius muscle increased 9% in response to training (p < 0.05) on the more-affected side. Passive hip flexion increased (p < 0.05) on the less-affected side and ankle dorsiflexion decreased (p < 0.05) on the more affected side after 12 weeks of RaceRunning training., Conclusions: These results support the efficacy of RaceRunning as a powerful and effective training modality in individuals with CP, promoting both cardiorespiratory and peripheral adaptations.

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 45min of cycling (n = 10; TD EX) or were enrolled as controls with no exercise (n = 10; TD CON). Blood was drawn before and 30min 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 (~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 ~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 amiR-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. [ABSTRACT FROM AUTHOR]