Abstract TP303: Perfluorocarbon Oxygent Limits Functional Impairment and Brain Damage Following Subarachnoid Hemorrhage

Abstract

Introduction: Subarachnoid hemorrhage (SAH) is the deadliest form of hemorrhagic stroke. Post-SAH vasospasm induces brain tissue hypoxia-ischemia resulting in brain injury and functional impairments. However, translational studies focused on post-SAH brain tissue oxygenation for functional improvements remain limited. We propose the use of Oxygent, a perfluorocarbon (PFC) based lipid emulsion oxygen carrier, as a promising therapy to improve post-SAH functional outcomes. Here we propose the use of Oxygent, a perfluorocarbon (PFC), as effective therapeutics. Oxygent-PFC comes as a lipid emulsion of micro-particles with great flexibility. The ultra-smaller size of these particles as compared to RBCs lets them flow even when there is just a trickle of residual plasma and efficiently deliver oxygen to prevent tissue damage. We tested the hypothesis that Oxygent-PFC would attenuate post-SAH functional and anatomical impairments. Methods: Adult C57BL/6 wildtype mice were subjected to the endoperforation model of SAH followed by an i.v injection of Oxygent-PFC or saline (9ml/kg at 6h after SAH). At 48h after SAH, mice were tested for functional outcomes followed by blood collection through cardiac puncture. Thereafter, mice were transcardially perfused, and brains were harvested to assess various immunohistochemical and biochemical outcomes. Results and Conclusion: We found that SAH resulted in significant neurologic and motor deficits while Oxygent-PFC treatment attenuated these functional deficits. There was a significant neuronal death after SAH as compared with the sham group and Oxygent-PFC prevented neuronal death. Moreover, mitochondrial activity as assessed by OXPHOS was markedly decreased after SAH while Oxygent-PFC treatment significantly improved the mitochondrial activity as compared to the vehicle-treated SAH group. These data show that Oxygent-PFC treatment preserves mitochondrial activity, dimmish tissue damage, and improve functional outcomes. Our novel preliminary study in SAH encourages us to investigate the mechanism of action of Oxygent-PFC and a comprehensive preclinical trial to test its efficacy in different animal models of SAH.