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Life
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Current Challenges in Human Space Flight
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Current Challenges in Human Space Flight

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Astrobiology".

Deadline for manuscript submissions: 20 February 2026 | Viewed by 10958

Special Issue Editors

Dr. Larry D. Sanford

E-Mail Website
Guest Editor
Department of Pathology and Anatomy, Eastern Virginia Medical School, Norfolk, VA 23507, USA
Interests: learning and memory; neurocircuits; neuroimmunology; sleep; spaceflight stress
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Richard A. Britten

E-Mail Website
Guest Editor
Department of Radiation Oncology, Eastern Virginia Medical School, Norfolk, VA 23507, USA
Interests: space radiation; radiobiology; cognitive testing; executive functions; neurocircuit

Special Issue Information

Dear Colleagues,

Humankind’s foray into space and eventual interplanetary expeditions present significant challenges that will require an understanding of the effects of living off-planet and our ability to adapt to or develop countermeasures for the unique conditions in outer space. Astronauts on space missions experience microgravity, psychological stress, sleep loss and disturbances, and exposure to potentially harmful environmental conditions (space radiation, lunar and Martian dust, and prolonged hypercapnia). Exposure to these factors may be repeated or prolonged, and they may interact in their effects across multiple physiological and functional systems, which likely will vary in men and women and with individual differences in resilience and vulnerability. Their impact on biological systems and the ability to respond/adapt to their deleterious effects will be a critical determinant of the long-term health of space travelers. Meaningful research on these issues will require collaborations across research fields that have not typically interacted, as well as approaches that consider the demands imposed on terrestrial organisms by the spaceflight environment.

The goal of this Special Issue is to provide a forum for research on the challenges of spaceflight. We welcome research contributions that address the effects of spaceflight stressors on the brain, nervous system, and physiology, reviews that address current knowledge in the field, and papers on theoretical and modeling approaches needed to advance the field. Topics covered may include any area relevant to the biological effects of space flight. Papers on technical and engineering approaches needed to understand and/or facilitate adaptive function during space travel are also welcome.

Dr. Larry D. Sanford
Prof. Dr. Richard A. Britten
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Life is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • cognition
  • microgravity
  • sleep
  • stress
  • Martian and lunar dust
  • neural stem cells and progenitors

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Published Papers (4 papers)

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Research

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16 pages, 3457 KiB  
Article
Galactic Cosmic Irradiation Alters Acute and Delayed Species-Typical Behavior in Male and Female Mice
by Stephanie Puukila, Olivia Siu, Linda Rubinstein, Candice G. T. Tahimic, Moniece Lowe, Steffy Tabares Ruiz, Ivan Korostenskij, Maya Semel, Janani Iyer, Siddhita D. Mhatre, Yasaman Shirazi-Fard, Joshua S. Alwood, Amber M. Paul and April E. Ronca
Life 2023, 13(5), 1214; https://doi.org/10.3390/life13051214 - 19 May 2023
Cited by 2 | Viewed by 2932
Abstract
Exposure to space galactic cosmic radiation is a principal consideration for deep space missions. While the effects of space irradiation on the nervous system are not fully known, studies in animal models have shown that exposure to ionizing radiation can cause neuronal damage [...] Read more.
Exposure to space galactic cosmic radiation is a principal consideration for deep space missions. While the effects of space irradiation on the nervous system are not fully known, studies in animal models have shown that exposure to ionizing radiation can cause neuronal damage and lead to downstream cognitive and behavioral deficits. Cognitive health implications put humans and missions at risk, and with the upcoming Artemis missions in which female crew will play a major role, advance critical analysis of the neurological and performance responses of male and female rodents to space radiation is vital. Here, we tested the hypothesis that simulated Galactic Cosmic Radiation (GCRSim) exposure disrupts species-typical behavior in mice, including burrowing, rearing, grooming, and nest-building that depend upon hippocampal and medial prefrontal cortex circuitry. Behavior comprises a remarkably well-integrated representation of the biology of the whole animal that informs overall neural and physiological status, revealing functional impairment. We conducted a systematic dose-response analysis of mature (6-month-old) male and female mice exposed to either 5, 15, or 50 cGy 5-ion GCRSim (H, Si, He, O, Fe) at the NASA Space Radiation Laboratory (NSRL). Behavioral performance was evaluated at 72 h (acute) and 91-days (delayed) postradiation exposure. Specifically, species-typical behavior patterns comprising burrowing, rearing, and grooming as well as nest building were analyzed. A Neuroscore test battery (spontaneous activity, proprioception, vibrissae touch, limb symmetry, lateral turning, forelimb outstretching, and climbing) was performed at the acute timepoint to investigate early sensorimotor deficits postirradiation exposure. Nest construction, a measure of neurological and organizational function in rodents, was evaluated using a five-stage Likert scale ‘Deacon’ score that ranged from 1 (a low score where the Nestlet is untouched) to 5 (a high score where the Nestlet is completely shredded and shaped into a nest). Differential acute responses were observed in females relative to males with respect to species-typical behavior following 15 cGy exposure while delayed responses were observed in female grooming following 50 cGy exposure. Significant sex differences were observed at both timepoints in nest building. No deficits in sensorimotor behavior were observed via the Neuroscore. This study revealed subtle, sexually dimorphic GCRSim exposure effects on mouse behavior. Our analysis provides a clearer understanding of GCR dose effects on species typical, sensorimotor and organizational behaviors at acute and delayed timeframes postirradiation, thereby setting the stage for the identification of underlying cellular and molecular events. Full article
(This article belongs to the Special Issue Current Challenges in Human Space Flight)
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16 pages, 1852 KiB  
Article
Sleep and Core Body Temperature Alterations Induced by Space Radiation in Rats
by Larry D. Sanford, Austin M. Adkins, Alea F. Boden, Justin D. Gotthold, Ryan D. Harris, Dorela Shuboni-Mulligan, Laurie L. Wellman and Richard A. Britten
Life 2023, 13(4), 1002; https://doi.org/10.3390/life13041002 - 13 Apr 2023
Cited by 3 | Viewed by 2280
Abstract
Sleep problems in astronauts can arise from mission demands and stress and can impact both their health and ability to accomplish mission objectives. In addition to mission-related physical and psychological stressors, the long durations of the proposed Mars missions will expose astronauts to [...] Read more.
Sleep problems in astronauts can arise from mission demands and stress and can impact both their health and ability to accomplish mission objectives. In addition to mission-related physical and psychological stressors, the long durations of the proposed Mars missions will expose astronauts to space radiation (SR), which has a significant impact on the brain and may also alter sleep and physiological functions. Therefore, in this study, we assessed sleep, EEG spectra, activity, and core body temperature (CBT) in rats exposed to SR and compared them to age-matched nonirradiated rats. Male outbred Wistar rats (8–9 months old at the time of the study) received SR (15 cGy GCRsim, n = 15) or served as age- and time-matched controls (CTRL, n = 15) without irradiation. At least 90 days after SR and 3 weeks prior to recording, all rats were implanted with telemetry transmitters for recording EEG, activity, and CBT. Sleep, EEG spectra (delta, 0.5–4 Hz; theta, 4–8 Hz; alpha, 8–12 Hz; sigma, 12–16 Hz; beta, 16–24 Hz), activity, and CBT were examined during light and dark periods and during waking and sleeping states. When compared to the CTRLs, SR produced significant reductions in the amounts of dark period total sleep time, total nonrapid eye movement sleep (NREM), and total rapid eye movement sleep (REM), with significant decreases in light and dark period NREM deltas and dark period REM thetas as well as increases in alpha and sigma in NREM and REM during either light or dark periods. The SR animals showed modest increases in some measures of activity. CBT was significantly reduced during waking and sleeping in the light period. These data demonstrate that SR alone can produce alterations to sleep and temperature control that could have consequences for astronauts and their ability to meet mission demands. Full article
(This article belongs to the Special Issue Current Challenges in Human Space Flight)
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71 pages, 483 KiB  
Perspective
Circuits and Biomarkers of the Central Nervous System Relating to Astronaut Performance: Summary Report for a NASA-Sponsored Technical Interchange Meeting
by Joshua S. Alwood, Ajitkumar P. Mulavara, Janani Iyer, Siddhita D. Mhatre, Susanna Rosi, Mark Shelhamer, Catherine Davis, Christopher W. Jones, Xiao Wen Mao, Rajeev I. Desai, Alexandra M. Whitmire and Thomas J. Williams
Life 2023, 13(9), 1852; https://doi.org/10.3390/life13091852 - 31 Aug 2023
Cited by 4 | Viewed by 2652
Abstract
Biomarkers, ranging from molecules to behavior, can be used to identify thresholds beyond which performance of mission tasks may be compromised and could potentially trigger the activation of countermeasures. Identification of homologous brain regions and/or neural circuits related to operational performance may allow [...] Read more.
Biomarkers, ranging from molecules to behavior, can be used to identify thresholds beyond which performance of mission tasks may be compromised and could potentially trigger the activation of countermeasures. Identification of homologous brain regions and/or neural circuits related to operational performance may allow for translational studies between species. Three discussion groups were directed to use operationally relevant performance tasks as a driver when identifying biomarkers and brain regions or circuits for selected constructs. Here we summarize small-group discussions in tables of circuits and biomarkers categorized by (a) sensorimotor, (b) behavioral medicine and (c) integrated approaches (e.g., physiological responses). In total, hundreds of biomarkers have been identified and are summarized herein by the respective group leads. We hope the meeting proceedings become a rich resource for NASA’s Human Research Program (HRP) and the community of researchers. Full article
(This article belongs to the Special Issue Current Challenges in Human Space Flight)
15 pages, 337 KiB  
Opinion
New Radiobiological Principles for the CNS Arising from Space Radiation Research
by Richard A. Britten and Charles L. Limoli
Life 2023, 13(6), 1293; https://doi.org/10.3390/life13061293 - 31 May 2023
Cited by 6 | Viewed by 1940
Abstract
Traditionally, the brain has been regarded as a relatively insensitive late-reacting tissue, with radiologically detectable damage not being reported at doses < 60 Gy. When NASA proposed interplanetary exploration missions, it was required to conduct an intensive health and safety evaluation of cancer, [...] Read more.
Traditionally, the brain has been regarded as a relatively insensitive late-reacting tissue, with radiologically detectable damage not being reported at doses < 60 Gy. When NASA proposed interplanetary exploration missions, it was required to conduct an intensive health and safety evaluation of cancer, cardiovascular, and cognitive risks associated with exposure to deep space radiation (SR). The SR dose that astronauts on a mission to Mars are predicted to receive is ~300 mGy. Even after correcting for the higher RBE of the SR particles, the biologically effective SR dose (<1 Gy) would still be 60-fold lower than the threshold dose for clinically detectable neurological damage. Unexpectedly, the NASA-funded research program has consistently reported that low (<250 mGy) doses of SR induce deficits in multiple cognitive functions. This review will discuss these findings and the radical paradigm shifts in radiobiological principles for the brain that were required in light of these findings. These included a shift from cell killing to loss of function models, an expansion of the critical brain regions for radiation-induced cognitive impediments, and the concept that the neuron may not be the sole critical target for neurocognitive impairment. The accrued information on how SR exposure impacts neurocognitive performance may provide new opportunities to reduce neurocognitive impairment in brain cancer patients. Full article
(This article belongs to the Special Issue Current Challenges in Human Space Flight)
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