Long-duration spaceflight may pose risks to brain

Changes in blood-based biomarkers suggested long-duration spaceflight may pose risks for humans, according to a research letter published in JAMA Neurology.

“[We sought to determine if] long-duration spaceflight or exposure to microgravity is potentially harmful for the brain,” Peter zu Eulenburg, MD, PhD, of the Institute for Neuroradiology, University Hospital, Ludwig-Maximilians-Universität, Munich, Germany, told Healio. “Our own MRI-based studies have suggested this, and we now use state-of-the-art blood-based biomarkers to delineate the brain-structural consequences of long missions aboard the International Space Station (ISS). This should be considered a pilot study in a small but exclusive sample.”

According to zu Eulenburg and colleagues, studies from the past decade showed eyeball alterations and potentially detrimental neural effects related to long-duration spaceflight, noting that the gray and white matter compartments are adversely affected by expansion of cerebrospinal fluid spaces. However, to their knowledge, no neurological integrity assessment has examined brain tissues after prolonged exposure to microgravity.

To address this research gap, they evaluated the longitudinal course of blood-based biomarkers that represented the brain parenchyma during long-duration spaceflight.

Blood samples were obtained from five male cosmonauts (mean age, 49.2 years) before and after missions that lasted a mean 169 days on the ISS between 2016 and 2020, with baseline data collection 20 days before launch. Sampling was then conducted 1 day, 1 week and 21 to 25 days after landing. Single-molecule array (Simoa) immunoassay quantification of neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), total tau and two amyloid-beta proteins was conducted, with hemoglobin as a control protein.

Results showed significantly elevated NfL directly after the flight, as well as 1 week and 3 weeks after return to Earth, compared with levels before the flight.

“The longitudinal course of hemoglobin as a systemic control protein for the blood-based analysis did not show any significant change or even trend over the same time course using the identical statistical approach in this cohort,” the researchers wrote.

GFAP increased at the end of the first week after the flight and beyond. During the first week, total tau had a nonsignificant elevation and then significantly dropped below baseline at 3 weeks after return. Amyloid-beta 40 significantly increased during the follow-up period. Amyloid-beta 42 levels had a similar but less significant increase.

NfL, GFAP and amyloid-beta 40 levels showed significant association with each other across the participants and times, according to correlation analyses. GFAP showed a correlation with NfL and amyloid-beta 40, and NfL with amyloid-beta 40. Amyloid-beta 40 and amyloid-beta 42 showed a correlation with each other. The researchers noted a significant correlation between each amyloid protein and the number of days from mission start.

“The immediate translational aspects of our study may be the role of the gravitational force vector for the cerebrospinal fluid circulation in general and the effect on brain-specific protein waste clearance in particular,” zu Eulenburg said.