Biomarkers for Damage to Brain tissue from Long Term F…: Neurology Today

Biomarkers for Damage to Brain tissue from Long Term F…: Neurology Today

When it comes to the neurologic risks of space flight, it’s not the take-off or the landing, but a prolonged period of weightlessness that poses the biggest problem. That’s the implication of a new study in in the October 11 online issue of JAMA Neurology that shows that, after months in space, blood markers of brain tissue damage are elevated upon reentry and remain so for weeks afterward.

“This study is important, first, because when we send astronauts into space, we are responsible for their safety,” commented Donna Roberts, MD, professor of radiology and radiologic medicine at the Medical University of South Carolina in Charleston. Dr. Roberts, who was not involved in the new study, has previously reported CNS structural anomalies from long-term space flight. “Second, as new programs are developing, including commercial ones, that are providing more opportunities for more people to go into space, and we have to make sure we are doing it safely.”

(Conversely, weightlessness may look like pure pleasure, but often triggers a day or two of motion sickness as the brainstem and cerebellum adjust to altered gravitational signals from the peripheral vestibular system.)

Short-term space flights, lasting hours to days or even weeks, appear to be safe, according to Peter zu Eulenburg, MD, PhD, lead author of the new study, based on the available literature on pre- and post-flight testing of both American astronauts and Russian cosmonauts. While lift-off may look excruciating to those on the ground, the excess forces from acceleration are relatively minor—about 7 G, or 7 times the force of gravity on earth, compared with as much as 100 G for a concussion-causing head-to-head collision in professional football.

Story Highlights

  • A study charting the effects of long-term space flight in five cosmonauts found changes in blood markers of brain injury and degeneration; the scientists said weightless in space may have led to the central nervous system changes.

  • The finding adds to a growing body of work showing that prolonged space flight has effects not just on the weight-bearing musculoskeletal system and the heart, but on the central nervous system (CNS) as well.

Previous studies have found structural changes in the CNS following long flights, specifically an increase in ventricular volume and displacement of the brain upwards, as well as a “spaceflight-associated neuro-ocular syndrome,” in which structural ocular changes including macular edema led to loss of visual acuity, which may not completely resolve back on earth.

“However,” Dr. zu Eulenburg said, “assessment of the integrity of the brain’s tissues after prolonged exposure to microgravity has never been conducted.”

Study Details Working with an international team including a member of the Institute of Biomedical Problems of the Russian Academy of Sciences in Moscow, Dr. zu Eulenburg, who is professor at the Institute for Neuroradiology at University Hospital at Ludwig-Maximilians-University in Munich, Germany, analyzed blood samples from five cosmonauts before and after they spent a mean of 169 days on the International Space Station.

The mean age of the cosmonauts was 49.2 years, older than an earlier generation of space travelers, but perhaps not surprising, Dr. Roberts noted, given the long training and multiple missions that career astronauts and cosmonauts experience today. The team assessed levels of neurofilament light chain (NfL), a marker of axonal integrity; glial fibrillary acidic protein (GFAP), a marker of activated astrocytes; total tau, a marker of neuronal damage; and amyloid beta 42 and 40. Because normal levels of these proteins tend to range widely between individuals, intra-individual comparisons were made among values before space flight and one day, one week, and three weeks after return. Hemoglobin was used as a control.

“We cant ignore the other factors that are part of space flight, including high G forces, increased exposure to radiation, loss of sleep, changes to sleep-wake cycles, exposure to a unique microbial environment, and higher CO2 in the atmosphere of the space station—there is so much about the space flight environment that is unique, it is hard to say that it is due to any one variable.”—DR. DONNA ROBERTS NfL levels, which ranged from 5-18 pg/mL at baseline, were elevated in all cosmonauts at re-entry, and continued to rise for another week in four of the five. By three weeks, NfL had returned close to baseline in three of the five, but continued to rise, albeit more slowly, in the other two. The mean values for the group were 11.4 pg/mL at baseline, and then 15.2, 17.2, and 15.2 pg/mL at the post-flight time points, each value statistically significant compared with baseline. At its peak, a week after landing, mean NfL in the blood was 50 percent higher than its pre-flight level.

Both amyloid-beta 42 and amyloid-beta 40 increased substantially post-flight, and were still elevated above baseline by the study’s end. The 42/40 ratio, a marker for brain aging, fell from baseline to one day post-flight, and remained low (indicative of an unfavorable trajectory), though with wide inter-individual variation. “This study is small, and needs to be replicated,” Dr. zu Eulenburg said, “but it has very robust data. We see signs of tissue damage after long-duration space flight.”

Total tau declined on average towards the end of the post-flight observation, with a slight elevation seen at day one and week one, but a sharp drop by week three. The final mean value was a significant 52 percent lower than the baseline value. The same pattern emerged in the group data for GFAP, with an elevation compared with baseline seen at day one post-landing, a further elevation at week one , and persistent plateau at week three. But there were large inter-individual differences in both the absolute levels and the patterns of change, and the mean changes over time were borderline but not statistically significant (p=0.08).