Effects of Microgravity on Cerebral Arterial, Venous, and Lymphatic Function: Implications for Elevated Intracranial Pressure--NNX16AC28G
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NOTE: Continuation of "Effects of Microgravity on Cerebral Arterial, Venous, and Lymphatic Function: Implications for Elevated Intracranial Pressure," grant #NNX13AN33G, due to PI move to Florida State University. Approximately 29% of astronauts on short-term (~2 wk) space shuttle flights and 60% on long-duration (~6 mo) missions to the International Space Station (ISS) are reported to have experienced some impairment in distant or near visual acuity. These visual disturbances have been hypothesized to be related to increases in intracranial pressure. Increases in intracranial pressure associated with spaceflight are thought to occur through the cephalad shift of intravascular and cerebrospinal fluids due to the loss of the head-to-foot gravity vector present on Earth. In regard to the vascular component, increases in cerebral blood flow and capillary fluid filtration could elevate fluid movement into the cranium, while impaired function of cerebral veins and lymphatics could impede intracranial fluid drainage out of the cranium. Therefore, the purpose of this proposal is to examine the effects of long-term spaceflight on the vasoconstrictor, mechanical, and structural properties of cerebral arteries, veins, and lymphatic vessels. Flight: The aim of this project is to investigate whether spaceflight on the ISS alters the blood-brain barrier in rodents, as indicated by ultrastructural examination of the cerebral capillary endothelium. To assess the changes that occur in the structure of the blood-brain barrier, 10-15 female C57BL/6 mice, 10-11 weeks old will be loaded into a transporter (Animal Enclosure Module AEM-T; 10 mice/side), and late-loaded into a SpaceX Dragon rocket. After ascent and docking to the ISS, the mice will be transferred via an Animal Access Unit (AAU) and Mouse Transfer Box (MTB) to 2 Habitats (AEM-X). The mice will be grouped into four experimental groups, each housed in one side of an AEM-X. The groups, as determined by another investigation, will consist of mice receiving intraperitoneal (i.p.) injection of saline vehicle (n=5), Tetanus Toxoid (TT) vaccine (n=5), CpG ODN adjuvant (n=5), or TT vaccine + CpG ODN adjuvant (n=5). After mice have been exposed to microgravity for a minimum of 2 weeks, animals for this study will be inoculated with an injection of phosphate buffered saline (n=5) or CpG ODN adjuvant (n=5); a third group of animals injected with the TT vaccine (n=5) may be utilized. Two weeks later (14 +/- 2 days), the mice will be sacrificed in the Materials Science Glovebox (MSG). Sacrificing will be achieved via i.p. injection of 100/10 mg/kg ketamine/xylazine anesthesia followed by exsanguination by cardiac puncture. Following blood collection and harvest of spleen for another research investigation, the animals will have heads removed. ............
