TREATMENT OF STROKE IN DEEP SPACE MISSIONS BY THE USE OF A NEUROPROTECTANT AUTO-INJECTOR

摘要

Stroke constitutes a time critical medical emergency due to a sudden loss of blood supply to the brain, which leads to death or disability. If this occurs during spaceflight it would seriously compromise the astronaut's ability to perform mission tasks or even compromise safety in the spacecraft environment. Astronauts that travel outside of the low earth's orbit protective magnetosphere for a longer period of time may have a higher risk of developing cardiovascular disease and therefore cerebrovascular incident. A novel neuroprotectant, "NA1", has shown promising results in the treatment of stroke in preclinical and clinical studies. However, NA1 is administered as an intravenous infusion (IV), and this approach would not be the most effective strategy for administration in space due to limited supplies, the availability of qualified medical personnel on the spacecraft and the challenges of performing any intravenous procedure in a microgravity environment. Therefore, there is an unmet need for alternatives to the IV route in order to administer NA-1 safely, effectively and rapidly in space without significant medical training. Hypothesis: We expect that an intramuscular injection of NA1, a method that may be suitable for microgravity conditions, could achieve effective therapeutic pharmacokinetic parameters and enable easy administration for nonmedical professionals. Methods: NA1 was administered via the intramuscular (IM) route and pharmacokinetic analysis was performed to determine the plasma concentration of NA1 using reverse phase high performance liquid chromatography (RP-HPLC) assay on rat plasma samples. NAl's effectiveness in stroke was evaluated in a permanent pial vessel occlusion (PVO) stroke model in rats. Animals were treated with a single injection of NA1 IM or IV or with placebo at 1 hour after stroke onset. Infarct volumes were assessed in a blinded manner at 24 hours. Results: An IM dose was identified that shows a comparable Cmax to the IV route,