In the first study to observe the phenomenon in humans, findings have revealed that following a stroke, muscles lose their most basic building blocks.
After a stroke, patients are sometimes unable to use the arm on the affected side, resulting in the arm being held close to the body, with the elbow flexed. Findings from a new study, led by Northwestern University and Shirley Ryan AbilityLab, have revealed that muscles lose sarcomeres – the smallest, most basic muscle building blocks – to adapt to this impairment.
For the study, the researchers imaged biceps muscles with three non-invasive methods, finding that stroke patients had fewer sarcomeres – which make up the length and width of muscle fibres – along the length of the muscle fibre, which led to a shorter overall muscle structure.
The team hopes this discovery can help improve rehabilitation techniques to rebuild sarcomeres, ultimately helping to ease muscle tightening and shortening.
The research has been published in the Proceedings of the National Academy of Arts and Sciences.
The impact of stroke on muscles
Sarcomeres comprise two main proteins – actin and myosin – and, when these proteins work together, they enable a muscle to contract and produce force. Although previous animal studies have found that muscles lose serial sarcomeres after a limb is immobilised in a cast, the phenomenon had not been demonstrated in humans before. Animal studies demonstrated muscles that were shorter because they lost serial sarcomeres, also became stiffer.
Senior author, Wendy Murray, professor of biomedical engineering at Northwestern’s McCormick School of Engineering, professor of physical medicine and rehabilitation at the Northwestern University Feinberg School of Medicine, and research scientist at the Shirley Ryan AbilityLab, said: “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. 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.”
“There is a classic relationship between force and length,” said Amy Adkins, a PhD student in Murray’s laboratory and the study’s first author. “Given that the whole muscle is composed of these building blocks, losing some of them affects how much force the muscle can generate.”
Using MRI to measure muscle volume, ultrasound to measure bundles of muscle fibres, and two-photon microendoscopy to measure the microscopic sarcomeres, the researchers imaged biceps from seven stroke patients and four healthy participants. They also compared imaging from the patients’ affected side to their unaffected side, as stroke patients are more affected on one side of their body.
The finding demonstrated that the stroke patients’ affected biceps had less volume, shorter muscle fibres, and comparable sarcomere lengths, and, after combining data across scales, the team found that affected biceps had fewer sarcomeres in series compared to the unaffected biceps. The differences between stroke patients’ arms were greater than in healthy participants’ arms, indicating that the differences were associated with stroke.
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.
“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.”