FINAL REPORTING [Ed. note February 2022; Compiled from Final Technical Report received November 2021]
Hind-limb unloading (HLU) has been an established technique modeling microgravity for over 40 years. Recent observations showed that astronauts on long-duration spaceflight missions develop visual defects. This program examined whether these could be duplicated in the rat HLS (hindlimb suspension) model. Also of interest were any effects on intracranial pressure and their possible connection to the observed visual changes. Overall, the project proved successful; within limits, the rat continues to be a useful translational animal model for spaceflight research. The use of the rat allows continuous recording of physiological measurements using indwelling technology leading to the collection of large amounts of data from freely behaving subjects.
In summary, the rats evidenced
• some, but not all, of the visual changes seen in long-duration astronauts.
• a small, but sustained increase in intracranial pressure (ICP) that appears to be time of day dependent in that differences between HLS and baseline ICP were greater during the animals’ rest period, leading to a decrease in the circadian rhythm amplitude of ICP.
• alterations in circadian timing. The reduction in the amplitude of the rhythm of ICP is consistent with results from the rhythms of Tb and EEG. Changes were also seen in the circadian mean and phasing of these rhythms. This type of circadian dysfunction is known to occur during spaceflight, and can lead to overall physiological and behavioral deficits.
There was a gender and also an age factor in the responses. Comparison of the responses between Young male and Young female rats showed that the effects were much smaller in female rats. Comparison between Old and Young male rats revealed larger effects in the older animals.
These observations are of interest because the increase in ICP during the rest period may also have led to a decreased turnover of CSF (cerebrospinal fluid) and/or other CNS (central nervous sytem) fluid exchanges. Such decreases over extended periods of time may have resulted in CNS inflammatory responses.
DECEMBER 2018 ANNUAL REPORT:
During this period of performance, the research team has concluded the collection of data from all cohorts. These included young males, young females (to examine possible gender differences), older males (to examine possible age effects) and, finally, older males exposed to a hypercapnic environment similar to that present on International Space Station (ISS). Older males were chosen for hypercapnic exposure as this group presented the most significant response to HLS. Analysis of the data from this group will allow us to determine if there is a role of increased CO2 exposure in the etiology of these visual changes.
Intracranial pressure, body temperature, and EEG were recorded via biotelemetry. Biotelemetry data have been collected from the young male, young female, older male, and older male hypercapnic cohorts. Data analysis is underway.
Additional measurements of visual system function including complete ophthalmic clinical exams and measurement of intraocular pressure by tonometry have been performed. The retinal imaging performed during this program included both fundus imaging with fluorescein angiography and optical coherence tomography (OCT). The tissue histology studies that will complement these data are underway.