In a new study of stroke patients, researchers have discovered that, in an attempt to adapt for an unusable arm, muscles actually lose sarcomeres — their smallest, most basic building blocks.
Patients that have suffered a stroke are often unable to use the arm on their affected side. Sometimes, they end up holding it close to their body, with the elbow flexed. Northwestern University and Shirley Ryan AbilityLab researchers found out why this happens.
Stacked end to end (in series) and side to side (in parallel), sarcomeres form the length and width of muscle fibres. By imaging biceps muscles with three noninvasive methods, the researchers found that stroke patients had fewer sarcomeres along the length of the muscle fibre, resulting in the muscle structure being shorter overall.
This finding is consistent with the common patient experience of abnormally tight, stiff muscles that resist stretching, and it suggests that changes in the muscle potentially amplify existing issues caused by stroke, which is a brain injury. The team hopes this discovery can help improve rehabilitation techniques to rebuild sarcomeres, ultimately helping to ease muscle tightening and shortening.
“This is the most direct evidence yet that chronic impairments, which place a muscle in a shortened position, are associated with the loss of serial sarcomeres in humans,” said senior author Wendy Murray. “Understanding how muscles adapt following impairments is critical to designing more effective clinical interventions to mitigate such adaptations and to improve function following motor impairments.”
Murray is a professor of biomedical engineering at Northwestern’s McCormick School of Engineering, a professor of physical medicine and rehabilitation at the Northwestern University Feinberg School of Medicine and research scientist at the Shirley Ryan AbilityLab. The research was completed in collaboration with Julius Dewald, professor of physical therapy and human movement sciences and of physical medicine and rehabilitation at Feinberg, professor of biomedical engineering at McCormick, and research scientist at Shirley Ryan AbilityLab.
Measuring just 1.5 to 4.0 micrometres in length, sarcomeres are made up of two main proteins: actin and myosin. When these proteins work together, they enable a muscle to contract and produce force. Even though previous animal studies have found that serial sarcomeres are lost from muscles after a limb is immobilised in a cast, the phenomenon had never before been demonstrated in humans. The animal studies found that the shorter muscles due to lost serial sarcomeres also became stiffer.
“There is a classic relationship between force and length,” explained first author Amy Adkins, a PhD student in Murray’s laboratory. “Given that the whole muscle is composed of these building blocks, losing some of them affects how much force the muscle can generate.”
To conduct the study in humans, the researchers combined three non-invasive medical imaging techniques: MRI to measure muscle volume, ultrasound to measure bundles of muscle fibers and two-photon microendoscopy to measure the microscopic sarcomeres.
Imaging opens new possibilities
Combining these technologies, the researchers imaged biceps from seven stroke patients and four healthy participants. As stroke patients are more affected on one side of their body, the researchers compared imaging from the patients’ affected side to their unaffected side as well as to images from the healthy participants.
In the stroke patients’ affected biceps, researchers found less volume, shorter muscle fibres and comparable sarcomere lengths. After combining data across scales, they found that affected biceps had fewer sarcomeres in series compared to the unaffected biceps. Greater differences between stroke patients’ arms than healthy participants’ arms were seen, indicating that stroke was the cause.
By combining medical imaging to better view muscle structure, the study also establishes that it is possible to study muscle adaptations in sarcomere number in humans. Prior to two-photon microendoscopy, human studies were limited either to examining dissected tissues in anatomy labs, which give imperfect insight into how muscles adapt to injury and impairment, measuring sarcomere lengths during surgery or from a muscle biopsy, which restricts who can participate in the study.
“In almost every facet of our world, there is an important relationship between how something is put together (its structure) and how it works (its function),” the researchers said. “Part of the reason medical imaging is such a valuable resource and clinical tool is that this is also true for the human body, and imaging gives us an opportunity to measure structure.”
Source: Northwestern University
Journal information: Adkins, A.N., et al. (2021) Serial sarcomere number is substantially decreased within the paretic biceps brachii in individuals with chronic hemiparetic stroke. PNAS. doi.org/10.1073/pnas.2008597118.
