Extracellular vesicle characteristics and micro RNA content in cerebral palsy and typically developed individuals at rest and in response to aerobic exercise.

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 (~25%, p \u3c 0.05) of EVs. At baseline, let-7a, let-7b and let-7e were downregulated in individuals with CP compared to TD (p \u3c 0.05), while miR-100 expression was higher, and miR-877 and miR-4433 lower in CP compared to TD after exercise (p \u3c 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 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 C

Spasticity, muscle strength and functional mobility in children with cerebral palsy and in typically developing children : A pilot study

Introduction: Cerebral palsy (CP) is a CNS related permanent disorder following a lesion on the developing brain. Spasticity and muscle weakness are the most commonly reported impairments. Aim: To describe spasticity measured instrumentally as the muscle resistance and muscle strength in children with CP and in typically developing children (TD), and explore the relationship between muscle resistance, muscle strength and functional mobility. Method: Measurements of the muscle resistance in plantarflexors with Neuroflexor®. Muscle strength measurements in the lower leg with a rig-fixed dynamometry in n= 4 children with CP and in n = 11 TD children. Timed Up and Go (TUG) test measured in seconds in 4 children with CP. Results: Mann- Whitney U test showed a significant increased muscle resistance in plantarflexors during a fast movement between children with CP and TD children (p = 0.044). It was significantly shown that the children with CP were weaker in their dorsiflexors compared to the group of TD children (p = 0,001). Analysis for muscle resistance and TUG was collected for 2 children with CP and therefore no correlation analysis could be made. Conclusion: This pilot study indicates that the children with CP were weaker in their dorsiflexors compared to TD children and that muscle resistance measured during a passive elongation was higher, but no statistically significant conclusion can be made due to few included numbers of participants

Spasticity, muscle strength and functional mobility in children with cerebral palsy and in typically developing children : A pilot study

Introduction: Cerebral palsy (CP) is a CNS related permanent disorder following a lesion on the developing brain. Spasticity and muscle weakness are the most commonly reported impairments. Aim: To describe spasticity measured instrumentally as the muscle resistance and muscle strength in children with CP and in typically developing children (TD), and explore the relationship between muscle resistance, muscle strength and functional mobility. Method: Measurements of the muscle resistance in plantarflexors with Neuroflexor®. Muscle strength measurements in the lower leg with a rig-fixed dynamometry in n= 4 children with CP and in n = 11 TD children. Timed Up and Go (TUG) test measured in seconds in 4 children with CP. Results: Mann- Whitney U test showed a significant increased muscle resistance in plantarflexors during a fast movement between children with CP and TD children (p = 0.044). It was significantly shown that the children with CP were weaker in their dorsiflexors compared to the group of TD children (p = 0,001). Analysis for muscle resistance and TUG was collected for 2 children with CP and therefore no correlation analysis could be made. Conclusion: This pilot study indicates that the children with CP were weaker in their dorsiflexors compared to TD children and that muscle resistance measured during a passive elongation was higher, but no statistically significant conclusion can be made due to few included numbers of participants

Spasticity, muscle strength and functional mobility in children with cerebral palsy and in typically developing children : A pilot study

Introduction: Cerebral palsy (CP) is a CNS related permanent disorder following a lesion on the developing brain. Spasticity and muscle weakness are the most commonly reported impairments. Aim: To describe spasticity measured instrumentally as the muscle resistance and muscle strength in children with CP and in typically developing children (TD), and explore the relationship between muscle resistance, muscle strength and functional mobility. Method: Measurements of the muscle resistance in plantarflexors with Neuroflexor®. Muscle strength measurements in the lower leg with a rig-fixed dynamometry in n= 4 children with CP and in n = 11 TD children. Timed Up and Go (TUG) test measured in seconds in 4 children with CP. Results: Mann- Whitney U test showed a significant increased muscle resistance in plantarflexors during a fast movement between children with CP and TD children (p = 0.044). It was significantly shown that the children with CP were weaker in their dorsiflexors compared to the group of TD children (p = 0,001). Analysis for muscle resistance and TUG was collected for 2 children with CP and therefore no correlation analysis could be made. Conclusion: This pilot study indicates that the children with CP were weaker in their dorsiflexors compared to TD children and that muscle resistance measured during a passive elongation was higher, but no statistically significant conclusion can be made due to few included numbers of participants

Extracellular vesicle characteristics and microRNA content in cerebral palsy and typically developed individuals at rest and in response to aerobic exercise

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 &amp;lt; 0.05) of EVs. At baseline, let-7a, let-7b and let-7e were downregulated in individuals with CP compared to TD (p &amp;lt; 0.05), while miR-100 expression was higher, and miR-877 and miR-4433 lower in CP compared to TD after exercise (p &amp;lt; 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]</p

Table2_Extracellular vesicle characteristics and microRNA content in cerebral palsy and typically developed individuals at rest and in response to aerobic exercise.XLSX

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 (∼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 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.</p

Image4_Extracellular vesicle characteristics and microRNA content in cerebral palsy and typically developed individuals at rest and in response to aerobic exercise.pdf

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 (∼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 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.</p

Table1_Extracellular vesicle characteristics and microRNA content in cerebral palsy and typically developed individuals at rest and in response to aerobic exercise.XLSX

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 (∼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 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.</p

Image2_Extracellular vesicle characteristics and microRNA content in cerebral palsy and typically developed individuals at rest and in response to aerobic exercise.pdf

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 (∼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 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.</p