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Long-duration exposure to microgravity appeared to expand the combined brain and cerebrospinal fluid (CSF) volumes of International Space Station astronauts, a longitudinal MRI study showed.

The sum of brain and CSF fluids increased by 2.0% (P<0.001) and remained elevated 1 year after spaceflight (1.7% increase; P<0.001), reported Larry Kramer, MD, of the University of Texas Health Science Center at Houston, and coauthors in .

"What we identified that no one has really identified before is that there is a significant increase of volume in the brain's white matter from pre-flight to post-flight," Kramer said in a statement. "White matter expansion, in fact, is responsible for the largest increase in combined brain and cerebrospinal fluid volumes post-flight."

Astronauts on long-duration spaceflight missions have been known to develop changes in ocular structure and function: an earlier study reported that up to 60% of International Space Station crew members experienced at least minimal subjective , with some vision changes persisting for years. Chronic exposure to elevated intracranial pressure during spaceflight may be a contributing factor, but underlying causes remain unknown.

"When you're in microgravity, fluid such as your venous blood no longer pools toward your lower extremities but redistributes headward," Kramer said. "That movement of fluid toward your head may be one of the mechanisms causing changes we are observing in the eye and intracranial compartment."

The ongoing program -- a collaboration of NASA, commercial spaceflight companies including SpaceX, and international space agencies -- aims to establish "sustainable exploration" of the moon as a prelude to travel to Mars. "Not surprisingly, there is strong interest in expanding our understanding of the long-term effects of space flight on the human brain, especially because trips to the moon are already planned, a human trip to Mars in the next decade is a possibility (which could take 6-8 months each direction), and extended stays in space are already a reality (cosmonaut Valeri Polyakov holds the record at 437 days for a single mission)," observed Michael Lev, MD, of Massachusetts General Hospital in Boston, in an .

A recent study suggested that prolonged microgravity may be associated with and spaceflight-associated neuro-optic syndrome, Lev noted. "These long-duration flights correlate with brain structural changes in both white matter and ventricular volume, like those found in the cohort studied by Kramer et al.," he wrote.

In their study, Kramer and colleagues conducted brain MRI on 11 astronauts with a mean age of 45 before they traveled to the International Space Station and 1, 30, 90, 180, and 360 days after they returned. Ten of the 11 astronauts were men. Time between pre-flight MRI and launch was 530 days, and mean duration of spaceflight was 171 days.

At post-flight day 1, MRI showed increased mean volumes in the brain (28 mL; P<0.001), white matter (26 mL; P<0.001), mean lateral ventricles (2.2 mL; P<0.001), and mean summated brain and CSF (33 mL; P<0.001), with corresponding increases in mean aqueductal stroke volume (14.6 μL; P=0.045) and mean CSF peak-to-peak velocity magnitude (2.2 cm/sec; P=0.01). Mean summated brain and CSF volumes were still increased 360 days after spaceflight (28 mL; P<0.001).

The changes in lateral ventricular volume and aqueductal CSF flow stroke volume resembled those associated with normal-pressure hydrocephalus, the Kramer team noted. "Glymphatic pathway dysfunction has been implicated in normal-pressure hydrocephalus and, if applicable in microgravity, it could help explain increased white matter free water in postflight astronauts," they wrote. Day 1 increases in mean aqueductal stroke volume and mean CSF peak-to-peak velocity magnitude returned to baseline by 1-year followup.

Six of 11 (55%) astronauts showed evidence of pituitary gland deformation from pre-flight to day 1 post-flight. Average midline pituitary height decreased from 5.9 to 5.3 mm (P<0.001).

"The dome of the pituitary gland is predominantly convex in astronauts without prior exposure to microgravity, but showed evidence of flattening or concavity post-flight," Kramer noted. "This type of deformation is consistent with exposure to elevated intracranial pressures."

Earlier studies of both astronauts and cosmonauts have shown structural changes in after prolonged spaceflight, Lev pointed out. "The observations in the study by Kramer et al not only confirm those earlier findings but also help explain them by demonstrating the following results: (a) persistent brain and ventricular volume expansion out to 1 year, (b) increased peak aqueductal CSF flow velocity analogous to that seen with normal-pressure hydrocephalus, and (c) depression of the pituitary gland in over half the astronauts studied," he wrote.

This study had limitations, the researchers noted. It had no age- or sex-matched control group, and the time delay between the pre-flight baseline imaging and launch (530 days) "was longer than ideal," they wrote. The researchers relied on literature-based normative data to help discriminate between the effects of aging versus spaceflight. The study also was limited to a subset of astronauts, which may not represent the entire long-duration astronaut population. There was also no attempt to correlate the volumetric changes to neurological or mental function.

While the intracranial effects of spaceflight may not have a direct application to terrestrially-based medicine, future microgravity-related research may improve understanding of CSF hydrodynamics and brain structural changes in diseases like normal-pressure hydrocephalus, they added.

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