Long-duration spaceflight was linked to changes in blood biomarkers of brain injury and degeneration, an international team of scientists said.
Blood values of five cosmonauts who spent an average of 169 days on the International Space Station showed alterations in neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), tau, and amyloid-beta, reported Peter zu Eulenburg, MD, PhD, of Ludwig-Maximilians-University Munich in Germany, and co-authors, in a JAMA Neurology research letter.
"This longitudinal pilot study in astronauts shows an increase in several blood-based brain-specific proteins after a long-duration mission compared with preflight baseline values," zu Eulenburg told MedPage Today. "It confirms the hypothesis that we derived from our neuroimaging analyses over the past 3 years: the previously detected structural alterations to the brain are not healthy and probably represent a slight but lasting brain injury upon return to Earth."
"We say lasting, because the increase in neurofilament light chains, GFAP, and the amyloid proteins can be seen from day 1 back on Earth up to 3 weeks postflight without a full return to baseline," he said.
"The underlying cause, cephalad fluid shift, seems to create a venous outflow obstruction for the entire head," zu Eulenburg observed. "This, in return, leads to an expanding cerebrospinal fluid compartment over time -- several months -- with increased intracranial pressure levels and changes in brain microcirculation."
Earlier studies have shown that long-duration exposure to microgravity resulted in expanded brain and cerebrospinal fluid volumes, which remained elevated for at least 1 year after returning to Earth. Structural changes in the eye also have been seen after long-duration spaceflight.
In their analysis, zu Eulenburg and colleagues examined longitudinal blood samples from five male cosmonauts who were aboard the International Space Station an average of 5.6 months between 2016 and 2020. Blood samples were drawn before their missions and immediately after return to Earth, and also at 1 week and approximately 3 weeks (21-25 days) after landing.
Compared with preflight levels, NfL, a marker of axonal injury, was significantly elevated directly postflight, 1 week, and 3 weeks after return to Earth. GFAP showed an increase at the end of the first week postflight and beyond, suggesting a concurrent astrocytic response.
Two variants of amyloid-beta protein, Aβ40 and Aβ42, showed significant postflight increases that lasted the entire 3-week observation period, with a stronger elevation in Aβ40. The ratio of Aβ42/Aβ40 had a downward trajectory after return to Earth; in the general population, this trajectory has been associated with unfavorable long-term brain health. Tau protein, as a marker for gray matter, dropped by more than 50% below baseline levels 3 weeks after return to Earth.
Correlation analyses revealed a significant association of NfL, GFAP, and Aβ40 levels with each other across participants and times. Each amyloid protein also was significantly correlated with the number of days from mission start.
"Taken together, our results point towards a slight but lasting brain injury and potentially accelerated neurodegeneration," zu Eulenburg said. "All relevant tissue types of the brain seem to be affected."
The findings could reflect coherent reparatory processes of intracranial pressure associations from cephalad fluid shift with subsequent restoration of the blood-brain barrier integrity, zu Eulenburg and co-authors noted. "We speculate the elevation of amyloid proteins back on Earth to represent a washout phase after months of hindered protein waste clearance since albumin has been shown to remain stable or even decrease."
"This is a terrific, important, timely effort as we move forward with spaceflight being routine; indeed, William Shatner at age 90 is heading into space this week," noted Michael Lev, MD, of Massachusetts General Hospital in Boston, who wasn't involved with the study. "That said, it's important to underscore that these findings in cosmonauts refer to long-duration spaceflight."
"It will be useful and important if future studies include imaging of the glial-lymphatic system," Lev told MedPage Today. "If prolonged microgravity causes disruption of the glymphatic system, this might have long-term implications for the development of sleep disturbances, neurodegenerative disorders, and other neurological disorders, especially given the described changes in beta-amyloid."
These changes suggest brain injury may be a previously unknown risk for humans in long-duration spaceflight, the researchers pointed out.
"Further studies into countermeasures against the effects of microgravity on the human brain are needed to minimize neurological risks for long-duration missions and before we start planning a trip to Mars," zu Eulenburg said.
Disclosures
This work was supported by the German Space Agency on behalf of the Federal Ministry of Economics and Technology/Energy, the ESA (ELIPS 3 and 4 and SciSpaceE programmes), and the Roscosmos Program of Fundamental Research of the Institute for Biomedical Problems in Moscow, Russia.
The researchers reported no disclosures.
Lev reported relationships with Takeda, Roche-Genentech, and GE.
