Rns60 Brain Protection In Mouse Ischemic Stroke Mitigates Plasma Tau And Cortical Microvascular Perfusion

Introduction: RNS60 is 0.9% saline solution hypothesized to contain oxygen nanobubbles. Recently, we showed that 13 days of RNS60 treatment after transient middle cerebral artery occlusion (tMCAo) preserves recovery of memory and reduces brain infarction, neuronal cell death, microglial activation, amyloid pathology, and white matter damage. Previously, we also demonstrated the relationship between white matter demyelination and circulating tau in tMCAo. Here we report that RNS60 decreases plasma tau and increases cortical microvascular perfusion (MVP). Methods: Male C57BL/6J mice, 3-4 months old, were randomly divided into sham surgery or unilateral 60-minute tMCAo. Each group was subdivided into three treatment arms, receiving daily intraperitoneal administration of 0.2 mL of RNS60, pressurized normal saline (PNS60), or normal saline (NS) starting 2 hours after surgery for 13 days. Treatment assignments were blinded throughout the study. To assess circulating tau, plasma was collected before surgery and on day 14 post-surgery (after MVP measurements). Animals were then euthanized to assess infarct volume using TTC staining. Results: RNS60 treatment significantly (p<0.05) reduced brain infarction by 90% compared to controls, reduced plasma tau by 74% of controls, and significantly (p<0.05) increased MVP in motor cortex by 38% and by 39% in the parietal cortex. Conclusion: RNS60-treated mice exhibit significant brain protection after ischemic stroke and display decreased plasma tau levels and a significant increase in microvascular perfusion. Ongoing studies are investigating whether increased MVP is due to activation of angiogenesis. These data further support the evaluation of RNS60 in clinical stroke trials.