Using Electrical Impedance Myography as a Biomarker of Muscle Deconditioning in Rats Exposed to Micro- and Partial-Gravity Analogs

Abstract

As astronauts prepare to undertake new extra-terrestrial missions, innovative diagnostic tools are needed to better assess muscle deconditioning during periods of weightlessness and partial gravity. Electrical impedance myography (EIM) has been used to detect muscle deconditioning in rodents exposed to microgravity during spaceflight or using the standard ground-based model of hindlimb unloading via tail suspension (HU). Here, we used EIM to assess muscle changes in animals exposed to two new models: hindlimb suspension using a pelvic harness (HLS) and a partial weight-bearing (PWB) model that mimics partial gravity (including Lunar and Martian gravities). We also used a simple needle array electrode in lieu of surface or ex vivo EIM approaches previously employed. Our HLS results confirmed earlier findings obtained after spaceflight and tail suspension. Indeed, one EIM measure (i.e., phase-slope) that was previously reported as highly sensitive, was significantly decreased after HLS (day 0: 14.60 ± 0.97, day 7: 11.03 ± 0.81, and day 14: 10.13 ± 0.55 | Deg/MHz|, p < 0.0001), and was associated with a significant decrease in muscle grip force. Although EIM parameters such as 50 kHz phase, reactance, and resistance remained variable over 14 days in PWB animals, we identified major PWB-dependent effects at 7 days. Moreover, the data at both 7 and 14 days correlated to previously observed changes in rear paw grip force using the same PWB model. In conclusion, our data suggest that EIM has the potential to serve as biomarker of muscle deconditioning during exposure to both micro-and partial-gravity during future human space exploration.

Relationships between in vivo surface and ex vivo electrical impedance myography measurements in three different neuromuscular disorder mouse models

“…We also note that there is a middle ground between ex vivo and surface measurements, namely measurement using indwelling needle electrodes. Needle electrodes could theoretically be placed subcutaneously or intramuscularly, but, to date, most of the work completed using needle electrode arrays has been performed intramuscularly [15,33,36,37]. In fact, placing needles subcutaneously is quite challenging, and even small variations in position could greatly impact the impedance data obtained.…”

Biomanufacturing in low Earth orbit for regenerative medicine

“…Thus, microgravity-induced muscle loss provides an opportunity to study muscle-wasting progression on a faster timescale than is possible on Earth. Multiple studies have been conducted using rodents in microgravity as an accelerated disease model to elucidate mechanisms underlying muscle atrophy and to test new potential therapeutics ( Chakraborty et al., 2020 ; da Silveira et al., 2020 ; Lawler et al., 2021 ; Semple et al., 2020 ; Smith et al., 2020 ). Moving beyond rodent models, microgravity provides a unique opportunity to study sarcopenia and disuse atrophy in human cellular models.…”

Opportunities for Biomanufacturing in Low Earth Orbit: Current Status and Future Directions

“…Finally, participants also agreed that interactions with the FDA should be part of refining a roadmap for biomanufacturing in space. mechanisms underlying muscle atrophy and to test new potential therapeutics (Lawler, J. M., et al 2021, da Silveira, W. A., et al 2020, Semple, C., et al 2020, Chakraborty, N., et al 2020. Moving beyond rodent models, microgravity provides a unique opportunity to study sarcopenia and disuse atrophy in a human cellular model.…”