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Pre-clinical Model of Cardiac Donation after Circulatory Death

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Resistance and Aerobic Preconditioning Delays Unloading-Induced Multisystemic Physiological Changes: The NEBULA

Théo Fovet^1,2, Margot Issertine³, Pauline Jacob⁴

¹SAINBIOSE-U1059, INSERM, Université Jean Monnet, Mines Saint-Etienne, Saint-Etienne, France.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology

|July 4, 2025

Summary

Pre-flight high-intensity training (PreC) significantly improved musculoskeletal health in mice. This preconditioning delayed microgravity-induced deconditioning, preserving bone and muscle structure and enhancing neurogenesis.

Keywords:

countermeasure hindlimb unloading multisystemic physical exercise preconditioning spaceflight

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Area of Science:

Spaceflight physiology
Exercise biology
Musculoskeletal adaptation

Background:

Spaceflight induces rapid physiological deconditioning.
Microgravity affects musculoskeletal, cardiovascular, immunological, and nervous systems.
Effective countermeasures are crucial for astronaut health.

Purpose of the Study:

To investigate if pre-flight high-intensity training (preconditioning) can mitigate initial microgravity-induced deconditioning.
To assess the systemic effects of preconditioning on musculoskeletal and nervous systems in a preclinical model.
To evaluate the impact of preconditioning on tendon integrity and immune function.

Main Methods:

Sixty male C57BL/6J mice underwent 3 weeks of high-intensity preconditioning (PreC) or served as controls (Ctrl).
Both groups were subjected to 7 or 21 days of hindlimb unloading (HU) to simulate microgravity.
Tissue and serum samples were analyzed post-preconditioning (HU0), after 7 days (HU7), and 21 days (HU21) of HU.

Main Results:

Preconditioning significantly enhanced physical performance, bone, and muscle mass/architecture at HU0.
Hindlimb unloading caused severe bone and muscle deconditioning by HU7 in controls, worsening by HU21.
Preconditioned mice maintained initial improvements through HU7, with decline by HU21; tendon and immune function remained unaffected.
Preconditioning prevented the decline in adult neurogenesis associated with intense exercise and microgravity.

Conclusions:

Pre-flight physical conditioning offers broad systemic benefits, delaying adverse effects of reduced mechanical loading.
Preconditioning shows potential as a countermeasure when prolonged exercise is not feasible.
Targeted preconditioning can support astronaut health during space missions and recovery.