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Space Biology Research Paper

Progress in four specific areas is profiled below, each of which is a NASA “Health and Human Performance Risk for Space Exploration”.8 All demonstrate linkages between basic and applied research and involve on-going collaborations between Space Biology and the HRP. These examples illustrate ongoing opportunities for synergy between basic and applied researchers and these NASA programs to enhance and accelerate health-risk reduction.

Immune response

The immune system is constantly adapting and is particularly responsive to unique environments such as those in spaceflight, especially for exposures of the long durations required by exploration missions beyond LEO. Immune system dysregulation (decreased responsiveness) has been seen during and after spaceflight and ground-space analog tests by studying humans,54 animals,55 and relevant cell cultures56 and are a priority area for study (AH13-15, Table 1). The specific causes are not yet clear, but are likely linked to one or more of the following factors: physiological stress, circadian rhythm disruption, microgravity exposure, isolation, altered nutrition, or radiation exposure.57 Further, the spaceflight environment compounds crew health risks as some microorganisms become more virulent (see below) and resistant to antibiotic drugs.

Even though the reactivation of latent viruses has been well documented in crewmembers,58 it is still unclear if the compromised immune response can lead to increased susceptibility to disease. There is not a sufficiently accurate ground-based analog to study immune suppression from spaceflight. However, extreme occupational environments such as Antarctica winter-over and the Aquarius undersea station enable aspects of immune dysregulation to be studied under similar stressors. Additionally, many valuable analog studies with animals and cells have been conducted, including unloading of rodents,59 and cell cultures and bioreactors.56,60 These studies have investigated immune response mechanisms and can allow the use of controlled diets, increased radiation levels and other factors that are not possible in human research.

Microbe-host interactions

Preventive measures limit the presence of many medically significant microorganisms during spaceflight missions, but microbial infection of crewmembers cannot be completely prevented. Spaceflight experiments have demonstrated unique and heterogeneous microbial responses in spaceflight ecosystems and cultures,61,62 although the mechanisms behind those responses and their operational relevance remain unclear. In 2007, the operational importance of these microbial responses increased, as the results of Space Biology experiments aboard STS-115 and STS-123 demonstrated that an enteric pathogen (Salmonella typhimurium) increased in virulence in a mouse model of infection,63,64 responding to recommendation AH15 (Table 1). These studies can improve our understanding of the potential consequences to astronauts of elevated microbial virulence during long-duration missions.

Evidence for increased microbial virulence has recently been collected and reported from both spaceflight-analog systems and actual spaceflight.61,65,66 Although the conduct of virulence studies during spaceflight is challenging and often impractical in humans, data are being collected as part of the ISS Microbial Observatory,62 recent astronaut and rodent microbiome studies,67,68,69 and the edible plant studies (e.g., Veggie).70,71 When available, these results can improve our understanding of the astronaut-microbe interaction and of the potential health risks to the astronaut.

Oxidative stress

The novel environmental conditions of spaceflight, and their combination, may affect both the generation and safe processing of reactive oxygen or nitrogen species.72,73 Evidence for oxidative-related issues in astronauts (or their analogs) can be found in the HRP Evidence Reports covering inadequate nutrition,74 extravehicular activity,75 and exposure to ionizing radiation.47,76,77,78,79 NASA has successfully used horizontally-integrated team science to understand and mitigate components of radiation-induced oxidative stress42,43,44 in mice.

Visual impairment/intracranial pressure (VI/IP)

During and after long-duration spaceflights, some astronauts have reported noticeable, persistent VIs accompanied by ophthalmic changes including globe flattening, choroidal folds, optic-disc edema, and optic-nerve kinking.80 To date, clinically significant changes have been observed in male, but not female, astronauts,81 identifying a not yet understood sex difference, CC10 (Table 2). Increased intracranial pressure and optic-disc swelling (papilledema) may underlie these potentially irreversible changes.81 Current research is analyzing the effects of lowering cranial hypertension by using lower body negative pressure in astronauts during flight and bedrest,82 supporting the CC2 goal (Table 2).

Clinical signs and symptoms observed in astronauts have informed and focused important mechanistic studies exemplifying reciprocal translation at NASA (i.e., applied to basic). For example, retinas of female mice flown on the shuttle (STS-133, STS-135), acquired by the BioSpecimen Sharing Program, exhibit altered gene expression and increased oxidative stress,83 possibly causing retinal damage, degeneration, or remodeling.84,85 Other basic research is examining morphological, histological, and molecular changes in the brains and eyes of rats exposed to head-down tilt.86

Altogether, these examples are in the early stages of mechanistic understanding and countermeasure development. Already each has benefited from translational approaches. We suggest that a more coordinated programmatic effort of horizontal and vertical integration will accelerate countermeasure development. In the closing section, we provide suggestions of how enhanced translational research could materialize at NASA.

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