Abstract 15737: Xenon Delivery Into Subarachnoid Hemorrhage via Echogenic Liposomes Provides Long-Term Neuroprotection
Background: Consequences of subarachnoid hemorrhage (SAH) including intracerebral bleeding and vasospasm result in permanent neurologic dysfunction or death. We have developed Xenon-containing echogenic liposomes (Xe-ELIP) and have demonstrated early cellular neuroprotection. We hypothesize that stabilizing cells in the neurovascular unit in the early stages of SAH provides long-term neurovascular benefit.
Methods: Xe-ELIP were prepared by a pressurization-freeze method. Sprague Dawley rats (n=90) were evaluated: sham, SAH with no treatment, and following SAH ELIP only @30 minutes, Xe-ELIP @30 minutes, ELIP only @2 hours, Xe-ELIP @2 hours, and Xe-ELIP in multiple doses. SAH was induced by an endovascular perforation method. All treatments were administrated intravenously for 5 minutes in combination with ultrasound application over the common carotid artery to trigger Xe release from the circulating Xe-ELIP. Xe concentration in the carotid arteries was measured using gas chromatography-mass spectroscopy (GC-MS). Blood-brain-barrier (BBB) permeability was measured using Evans Blue at 48 hours after SAH. Neurologic behavioral tests were performed at days 3, 7, 21, and 35. Mortality up to 35 days was determined.
Results: GC-MS detected a concentration (0.066 mM) of Xe in the carotid arteries following injection. Xe-ELIP @30 minutes and in multiple doses demonstrated the largest reduction of BBB permeability. These two treatments revealed reduced long-term mortality (Fig. 1). Behavioral test improvements followed the decrease in hemorrhage in the treatment groups.
Conclusions: Ultrasound-facilitated Xe delivery using Xe-ELIP demonstrated Xe delivery to the cerebral circulation, alleviated early brain injury following SAH, and reduced long-term mortality and neurologic impairment. This novel therapy has the potential to be given in the field for immediate neurovascular protection with lasting effect.
Author Disclosures: T. Peng: None. N. Zeng: None. E.R. Migliati: None. M.R. Moddy: None. M.E. Klegerman: Ownership Interest; Modest; Zymo Pharmaceuticals, LLC. H. Kim: Ownership Interest; Modest; Zymo Pharmaceuticals, LLC. X. Yin: None. Y. Geng: Ownership Interest; Modest; zymo Pharmaceuticals, LLC. D.D. McPherson: Ownership Interest; Modest; Zymo Pharmaceuticals, LLC. J. Aronowski: None. S. Huang: Ownership Interest; Modest; Zymo Pharmaceuticals, LLC.
- © 2014 by American Heart Association, Inc.