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Study · Animal study (in vivo) · mouse · 2024

1 result

Post-sepsis chronic muscle weakness can be prevented by pharmacological protection of mitochondria.

Kingren MS, Keeble AR, Galvan-Lara AM, Ogle JM, Ungvári Z, St Clair DK, Butterfield TA, Owen AM, Fry CS, Patel SP, Saito H

Molecular medicine (Cambridge, Mass.)19 Nov 2024Cited by 14 (Europe PMC)

PMID39563237 (opens in a new tab)PMCIDPMC11577827 (opens in a new tab)DOI10.1186/s10020-024-00982-w (opens in a new tab)PepBankPUB-39563237
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Summary

BackgroundSepsis, mainly caused by bacterial infections, is the leading cause of in-patient hospitalizations. After discharge, most sepsis survivors suffer from long-term medical complications, particularly chronic skeletal muscle weakness. To investigate this medical condition in detail, we previously developed a murine severe sepsis-survival model that exhibits long-term post-sepsis skeletal muscle weakness. While mitochondrial abnormalities were present in the skeletal muscle of the sepsis surviving mice, the relationship between abnormal mitochondria and muscle weakness remained unclear. Herein, we aimed to investigate whether mitochondrial abnormalities have a causal role in chronic post-sepsis muscle weakness and could thereby serve as a therapeutic target.MethodsExperimental polymicrobial abdominal sepsis was induced in 16-18 months old male and female mice using cecal slurry injection with subsequent antibiotic and fluid resuscitation. To evaluate the pathological roles of mitochondrial abnormalities in post-sepsis skeletal muscle weakness, we utilized a transgenic mouse strain overexpressing the mitochondria-specific antioxidant enzyme manganese superoxide dismutase (MnSOD). Following sepsis development in C57BL/6 mice, we evaluated the effect of the mitochondria-targeting synthetic tetrapeptide SS-31 in protecting mitochondria from sepsis-induced damage and preventing skeletal muscle weakness development. In vivo and in vitro techniques were leveraged to assess muscle function at multiple timepoints throughout sepsis development and resolution. Histological and biochemical analyses including bulk mRNA sequencing were used to detect molecular changes in the muscle during and after sepsis RESULTS: Our time course study revealed that post sepsis skeletal muscle weakness develops progressively after the resolution of acute sepsis and in parallel with the accumulation of mitochondrial abnormalities and changes in the mitochondria-related gene expression profile. Transgenic mice overexpressing MnSOD were protected from mitochondrial abnormalities and muscle weakness following sepsis. Further, pharmacological protection of mitochondria utilizing SS-31 during sepsis effectively prevented the later development of muscle weakness.ConclusionsOur study revealed that the accumulation of mitochondrial abnormalities is the major cause of post-sepsis skeletal muscle weakness. Pharmacological protection of mitochondria during acute sepsis is a potential clinical treatment strategy to prevent post-sepsis muscle weakness.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study1

1 result from studies that gave the peptide. No result from this study comes from people.

  1. 01AnimalAnimal study (in vivo)Efficacy outcome

    In mice that survived sepsis, SS‑31 given during sepsis effectively prevented the later development of muscle weakness.

    In plain wordsIn mice that survived sepsis, SS‑31 given during sepsis prevented muscle weakness from developing later.

    Peptide
    Elamipretide (SS-31)
    Outcome
    DecreasePost-sepsis skeletal muscle weakness
    Study

    mousen: not reported in source

    Cecal slurry polymicrobial sepsis survival model
    Outcome group
    Muscle injury and repair · Musculoskeletal
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Further, pharmacological protection of mitochondria utilizing SS-31 during sepsis effectively prevented the later development of muscle weakness.
    1 context sentence
    Summary · context
    Following sepsis development in C57BL/6 mice, we evaluated the effect of the mitochondria-targeting synthetic tetrapeptide SS-31 in protecting mitochondria from sepsis-induced damage and preventing skeletal muscle weakness development.

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Version history

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  1. Version 2Current

    10 Oct 2026, 08:19 UTC

    Study results updated

  2. Version 1

    9 Oct 2026, 02:47 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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