Spaceflight induces oxidative damage to blood-brain barrier integrity in a mouse model

FASEB J. 2020 Nov;34(11):15516-15530. doi: 10.1096/fj.202001754R. Epub 2020 Sep 26.


Many factors contribute to the health risks encountered by astronauts on missions outside Earth's atmosphere. Spaceflight-induced potential adverse neurovascular damage and late neurodegeneration are a chief concern. The goal of the present study was to characterize the effects of spaceflight on oxidative damage in the mouse brain and its impact on blood-brain barrier (BBB) integrity. Ten-week-old male C57BL/6 mice were launched to the International Space Station (ISS) for 35 days as part of Space-X 12 mission. Ground control (GC) mice were maintained on Earth in flight hardware cages. Within 38 ± 4 hours after returning from the ISS, mice were euthanized and brain tissues were collected for analysis. Quantitative assessment of brain tissue demonstrated that spaceflight caused an up to 2.2-fold increase in apoptosis in the hippocampus compared to the control group. Immunohistochemical analysis of the mouse brain revealed an increased expression of aquaporin4 (AQP4) in the flight hippocampus compared to the controls. There was also a significant increase in the expression of platelet endothelial cell adhesion molecule-1 (PECAM-1) and a decrease in the expression of the BBB-related tight junction protein, Zonula occludens-1 (ZO-1). These results indicate a disturbance of BBB integrity. Quantitative proteomic analysis showed significant alterations in pathways responsible for neurovascular integrity, mitochondrial function, neuronal structure, protein/organelle transport, and metabolism in the brain after spaceflight. Changes in pathways associated with adhesion and molecular remodeling were also documented. These data indicate that long-term spaceflight may have pathological and functional consequences associated with neurovascular damage and late neurodegeneration.

Keywords: blood-brain barrier; brain tissue; microgravity; neurodegeneration; proteomics; spaceflight.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Apoptosis
  • Biological Transport
  • Blood-Brain Barrier / metabolism
  • Blood-Brain Barrier / pathology*
  • Blood-Brain Barrier / radiation effects
  • Brain / metabolism
  • Brain / pathology*
  • Brain / radiation effects
  • Disease Models, Animal*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mitochondria / metabolism
  • Mitochondria / pathology*
  • Mitochondria / radiation effects
  • Oxidative Stress / radiation effects*
  • Proteome / analysis*
  • Proteome / radiation effects
  • Space Flight / methods*
  • Weightlessness


  • Proteome