Onset of neonatal locomotor behavior and the mechanical development of Achilles and tail tendons

Theodossiou, Sophia K.; Bozeman, Aimee L.; Burgett, Nicholas; Brumley, Michele R.; Swann, Hillary E.; Raveling, Abigail R.; Becker, Jordan J.; Schiele, Nathan R.

doi:10.1016/j.jbiomech.2019.109354

Cited by 16 publications

(23 citation statements)

References 53 publications

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“…It is curious and interesting that we found no effects related to hindlimb activity. Perhaps this is because rat pups have relatively small hindlimbs at birth, and still are not showing much weight‐bearing movement within the first few postnatal days (Theodossiou et al., 2019 ). Perhaps if this study were protracted out to a later developmental time point, we would have observed deficits in hindlimb movement, as have been shown in posthatch chicks (Khan et al., 2017 ).…”

Section: Discussionmentioning

confidence: 99%

A preliminary investigation of high retinoic acid exposure during fetal development on behavioral competency and litter characteristics in newborn rats

et al. 2021

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Myelomeningocele (MMC) is the most common and severe type of spina bifida in which the developing spine and neural tube fail to close during prenatal development. This typically results in a small portion of the lower spinal cord and meninges protruding from the back of the individual, accompanied by severe motor and sensory deficits.In rats, retinoic acid (RA) exposure in high doses during fetal development has been shown to induce morphologic and clinical symptoms similar to humans with MMC. The aim of the current study was to examine litter characteristics and sensorimotor function in MMC-affected rat pups. Pregnant rats were gavage-fed 2 ml olive oil or alltrans RA (40, 45, 50 mg/kg) on gestational day 11. Pups underwent behavioral testing on postnatal day 2. Litter characteristics and newborn sensorimotor function varied across RA doses. Pups prenatally exposed to 45 and 50 mg/kg RA weighed significantly less than olive oil and 40 mg/kg RA pups. Litters exposed to 45 mg/kg RA suffered significantly higher mortality rates compared to other groups. Additionally, bladder function was significantly impaired in pups exposed to 40 mg/kg RA. Sensorimotor function findings demonstrated that for most behavioral assessments there was not a significant difference between control and RA-exposed subjects. However, pups treated with 40 mg/kg RA showed increased facial wiping, suggesting a hyper-responsiveness to sensory stimuli. Overall, the findings of the current study provide evidence for a model to examine litter characteristics and behavioral effects as well as morphology.

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Section: Discussionmentioning

confidence: 99%

A preliminary investigation of high retinoic acid exposure during fetal development on behavioral competency and litter characteristics in newborn rats

et al. 2021

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“…Mouse embryos or limb bud grafts lacking skeletal muscles show degenerated or absent tendons (Kardon, 1988), and muscle paralysis in chick embryos from E6 to E18 reduces tendon size (Germiller et al, 1998). Interestingly, motility peaks in chicken embryos starting at E12 (Wu et al, 2001) and in neonatal rats at P10 (Theodossiou et al, 2019), suggesting that muscle activity may play a particularly important role in driving the rapid structural and mechanical changes observed during late tendon development. Indeed, a recent study demonstrated that I n r e v i e w immobilizing the developing chick embryo at later stages (HH43; generally equivalent to E17) resulted in a reduction in the compressive modulus of the calcaneal tendon measured via atomic force microscopy (Pan et al, 2018).…”

Section: N R E V I E W Mergeformatmentioning

confidence: 99%

Mechanical Stimulation via Muscle Activity is Necessary for the Maturation of Tendon Multiscale Mechanics during Embryonic Development

Peterson

Rolfe

Kunselman

et al. 2021

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During embryonic development, tendons transform into a hypocellular tissue with robust tensile load-bearing capabilities. Previous work suggests that this mechanical transformation is due to increases in collagen fibril length and is dependent on mechanical stimulation via muscle activity. However, the relationship between changes in the microscale tissue structure and changes in macroscale tendon mechanics is still unclear. Additionally, the specific effect of mechanical stimulation on the multiscale structure-function relationships of developing tendons is also unknown. Therefore, the objective of this study was to measure the changes in tendon mechanics and structure at multiple length scales during embryonic development with and without skeletal muscle paralysis. Tensile testing of tendons from chicken embryos was performed to determine the macroscale tensile modulus as well as the magnitude of the fibril strains and interfibrillar sliding with applied tissue strain. Embryos were also treated with either decamethonium bromide or pancuronium bromide to produce rigid or flaccid paralysis. Histology was performed to assess changes in tendon size, spacing between tendon subunits, and collagen fiber diameter. We found that the increase in the macroscale modulus observed with development is accompanied by an increase in the fibril:tissue strain ratio, which is consistent with an increase in collagen fibril length. Additionally, we found that flaccid paralysis reduced the macroscale tendon modulus and the fibril:tissue strain ratio, whereas less pronounced effects that were not statistically significant were observed with rigid paralysis. Finally, skeletal paralysis also reduced the size of collagen fibril bundles (i.e., fibers). Together, these data suggest that more of the applied tissue strain is transmitted to the collagen fibrils at later embryonic ages, which leads in an increase the tendon macroscale tensile mechanics. Furthermore, our data suggest that mechanical stimulation during development is necessary to induce structural and mechanical changes at multiple physical length scales. This information provides valuable insight into the multiscale structure-function relationships of developing tendons and the importance of mechanical stimulation in producing a robust tensile load-bearing soft tissue.

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“…Understanding the impacts of mechanical stimuli on musculoskeletal tissue formation during embryonic and neonatal development is of great interest [12] , [13] . Recent work has explored how paralysis [14] and the onset of locomotor behavior impacts tendon formation in the developing embryo and neonate, respectively [15] . Furthermore, physical activity by the developing neonate has long-term beneficial impacts on muscle mass and levels of inflammatory cytokines at later ages [16] .…”

Section: Hardware In Contextmentioning

confidence: 99%

Low-cost, open-source, variable speed and incline treadmill for studying impacts of neonatal locomotion

et al. 2020

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Onset of neonatal locomotor behavior and the mechanical development of Achilles and tail tendons

Cited by 16 publications

References 53 publications

A preliminary investigation of high retinoic acid exposure during fetal development on behavioral competency and litter characteristics in newborn rats

A preliminary investigation of high retinoic acid exposure during fetal development on behavioral competency and litter characteristics in newborn rats

Mechanical Stimulation via Muscle Activity is Necessary for the Maturation of Tendon Multiscale Mechanics during Embryonic Development

Low-cost, open-source, variable speed and incline treadmill for studying impacts of neonatal locomotion

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