Space is hostile to humans. Several environmental stressors – chiefly microgravity – impact astronaut health, hindering space exploration. The nervous system appears to be among the most affected apparatuses, the more so for the brain. The most obvious phenomenon is perhaps an upward redistribution of bodily fluids, which leads to increased intracranial pressure and ventricular size, with symptoms that may persist even after landing. But other factors are known or expected to contribute to brain pathology in space. Anatomically speaking, a notable brain structure is the blood-brain barrier (BBB), a selective boundary lining up the central nervous system. It covers microvessels surrounding the brain, regulating its physiological metabolism and protecting it from neurotoxins and pathogens. BBB leakage can cause metabolic disorders, anomalous fluid movement, and permeation of toxic compounds. In space, the physical alterations experienced by astronauts and the repercussion on their cognitive/behavioral skills suggest an involvement of the BBB. Even with several studies dedicated to endothelial cells in microgravity, however, little is known about endothelial cell response to reduced gravity when these compose a BBB. The paucity of space-apt models for the study of the BBB is likely among the causes of such void of knowledge. To aid future BBB research in space, we aim to develop an in vitro BBB mockup model usable in microgravity, which we will simulate via random positioning machine. Expectably, the device will allow the investigation of BBB adaptations to space per se, but will also open up the possibility of studying how microgravity influences brain treatment, such as drug delivery. Experience gathered aboard the International Space Station confirms brain-relevant pharmacokinetics, which include fundamental drug classes like anti-inflammatories and painkillers, to be especially relevant for a long-term human permanence in space.