Week 6 Reading Flashcards
What is muscle spasticity
a condition where muscles become stiff, tight, and difficult to control due to continuous, involuntary muscle contractions.
What does muscle spasticity lead to?
leads to muscle contractures that limit range of motion and cause increased muscle stiffness
what is titin
a major load bearing protein within muscle fibers
why do children with spastic cerebral palsy develop hamstring contractures
due to a stiffer extracellular matrix (ECM) and longer sarcomeres in their muscles
What did the study find?
while individual muscle fibers and the titin protein (which helps muscles stretch) were unchanged, the ECM was stiffer due to increased collagen.
what does cerebral palsy result from?
an upper motoneuron lesion in the developing brain
What did the combination of increased tissue stiffness and increased sarcomere length lead to?
leads to higher muscle tension and contractures
What did they find was the cause of contracture formation?
Stiffening of the ECM with increased collagen and an increase of in vivo sarcomere length - leading to higher passive strength
what is spastic
a velocity dependent resistance to stretch due to reduced inhibition of the stretch reflexes
what do children with CP experience?
contractures that limit their range of motion, decrease mobility, and cause pain
what is contracture?
a muscle adaptation where the muscle increases passive stiffness where the range of motion around a joint is limited without active force production of the muscle
- meaning: the muscle becomes stiffer and less flexible without the muscle actively contracting (even if ur not trying to use it)
What did this study compare? to find what?
hamstring muscles from children with CP to those from non-CP children undergoing surgery, aiming to identify what causes increased muscle stiffness in CP.
potential explanation for why spasticity results in contractures:
spastic muscles from children with CP are weaker than those of developing control children bc of a combination of decreased neuronal drive, decreased muscle size, and decreased specific tension
how does caffeine increase tension of isolated muscles?
Caffeine induces calcium release from the sarcoplasmic reticulum and potassium depolarizes the muscle as methods to activate the crossbridge cycle that produces muscle active tension
(cross bridge cycle is where the fibers generate contractions)
whats different about contractures from our normal contractions?
our muscles normally contract all the time, but in a controlled and voluntary way.
In contractures, the stiffness is passive—the muscle remains tight even without active contraction, meaning the restriction in movement is due to structural changes in the muscle, rather than the usual processes of voluntary movement.
what do they think contracture results from?
shortened muscles - they did multiple ultrasounds to measure fasciae length and only confirmed reduced CP muscle volume.
what is a major drawback of ultrasound studies?
there is no normalization of fascicle length to sarcomere length
What did direct measurement of intraoperative sarcomere length reveal
They revealed that sarcomere lengths are indeed longer in CP muscle, suggesting increased passive stiffness.
When sarcomeres are too long, the muscle becomes less able to stretch and contract effectively, leading to stiffness and reduced range of motion (contracture).
(bc their length determines how much a muscle can stretch and contract effectively AND SO in children with CP, muscles do not grow normally due to impaired neural control. Instead of having more short sarcomeres in series (which would allow for flexibility), the existing sarcomeres stretch longer to compensate for the muscle’s restricted length which is associated with increased passive stiffness.
explain the theory for increased passive stiffness that involves the alteration of the tissue itself
Studies found that individual muscle fibers from contractured muscles were stiffer than normal ones, suggesting that something inside the muscle cell was altered. They hypothesized that titan was the cause. After looking at bundles of muscle fibers, they found these were actually more flexible than normal which meant the stiffness wasn’t due to titin.
Researchers hypothesize that the stiffness might be due to changes at multiple levels including:
- protein (titin)
- cellular (fibre)
- tissue (fibre bundle)
- architecture (sarcomere length)
What were custom muscle biopsy clamps used for?
to determine in vivo sarcomere length in children with cerebral palsy (CP) undergoing hamstring lengthening surgery.
What steps were taken to prepare the gracilis and semitendinosus muscles for sarcomere length measurement?
After a skin incision, the muscles were identified, a small segment was isolated atraumatically, and the custom clamp was applied without tension on the muscle.
How was the muscle biopsy preserved after being resected?
The muscle section within the jaws of the clamp was immediately placed in Formalin to fix the biopsy specimen in its in vivo configuration.
For muscle mechanical testing - they stretched the muscle fibers, measured the mechanical properties, and recorded stress relaxation during the stretches
1. what was measured during each stretch?
2. how much were the fibers stretched
- stress relaxation
- 100% strain
How did researchers quantify titin isoforms? What were titin standards obtained from?
They looked at the molecular mass of titin in muscle samples using SDS-VAGE.
Obtained from human cadaver soles and rat cardiac muscle.
How did researchers quantify MyCh isoform distribution in muscle samples? How did they read the results? (MyCH = Myosin Heavy Chain isoforms, refer to different forms of the myosin protein found in muscle fibers)
They used BCA protein assay to measure protein concentration, then resuspended the protein in a sample buffer.
The gels were run at a constant current and voltage, followed by silver staining to visualize MyHC bands.
Progression of the band was compared and identified based on its relative molecular weight to that of a human protein standard prepared from a normal semitendinosus biopsy that showed all three human MHC bands (IIa, IIx and I)
^ that means: the researchers compared the bands they obtained from their protein samples to a “standard” protein sample. The standard was created from a normal human semitendinosus biopsy (a muscle from the back of the thigh), which showed the three main MyHC isoforms (Type I, IIa, and IIx). These isoforms have different molecular weights, so by comparing the molecular weights of the bands in the test samples to the known weights of the standard proteins, they could identify which MyHC isoform was present in the sample.
