Abstract WP433: Haemostatic and Neuroprotective Effects of Xe-loaded Echogenic Liposomes in a Subarachnoid Hemorrhagic Stroke Model

Abstract

Background: We have developed Xe-containing echogenic liposomes (Xe-ELIP). Using this delivery agent, we have demonstrated neuroprotective effects in an ischemic stroke model. Given the common mediators of cellular injury in ischemic and early-stage hemorrhagic stroke, the goal of this study was to evaluate the neuroprotective effects of Xe-ELIP on early brain injury after subarachnoid hemorrhage (SAH). Methods: Xe-ELIP was prepared by a pressurization-freeze method. The neuroprotective effects of Xe-ELIP on cultured brain astrocytes and microglia were evaluated by a lactate dehydrogenase (LDH) assay. For in vivo evaluation, rats (n=35) were randomly divided into sham, SAH, SAH with Xe-ELIP, ELIP treatment, and Xe saturated saline treatment groups. SAH was induced by an endovascular puncture method. Treatments were administrated intravenously in combination with ultrasound application over the common carotid artery to trigger Xe release from circulating Xe-ELIP at 30 minutes after SAH. Mortality assessments, neurological evaluations, and behavioral tests were conducted for three days following surgery. Brain tissue was harvested for SAH grading, H&E staining, TUNEL staining, and brain water content measurement on the third day after surgery. Results: Treatment with Xe-ELIP protected brain astroacytes and microglia against H 2 O 2 (10 mM) induced cytotoxicity. SAH grading revealed effective reduction of bleeding in association with decreased mortality. Moreover, Xe-ELIP significantly reduced apoptotic neuronal death and improved both general neurological and motor function. Conclusions: Xe-ELIP alleviates early SAH brain injury by inhibiting neuronal death and bleeding. This novel delivery approach, using Xe-ELIP with ultrasound-controlled cerebral drug release, provides a relatively noninvasive strategy for therapeutic gas delivery in SAH.