Abstract 5502: Ultrasound-Controlled Therapeutic Gas Delivery Provides Enhanced Neuroprotection Following Hypoxic-Ischemia
Background: Neurologic damage following ischemic insult is a major problem for stroke survivors. Xenon (Xe) exerts favorable neuroprotective properties with few side effects. This study describes a unique application of ultrasound for controlled release of Xe from liposomes (Xe-ELIP) for targeted therapeutic gas delivery and neuroprotection.
Method: Xe-ELIP were created by a pressurization-freezing method. One-MHz continuous ultrasound wave with pressure amplitudes of 0.16, 0.22 and 0.33 MPa was used to trigger Xe release from Xe-ELIP, and endothelial cell permeability and cell viability were measured. Male Sprague-Dawley rats underwent right middle cerebral artery occlusion for 2 hours (n=28). In the treatment group (n=8), Xe-ELIP were administered through the right common carotid artery. Continuous ultrasound (0.22 MPa) was applied over the common carotid artery during the Xe-ELIP administration for 4 minutes. Infarct size as well as behavioral outcomes were determined 3 days after treatments.
Results: Ultrasound application in the presence of ELIP resulted in a temporary (5 minutes) enhancement of cell permeability. The amount of released Xe depended on the ultrasound pressure amplitude. Xe-ELIP in combination with ultrasound exposure (0.22 MPa) enhanced neuroprotection by decreasing infarct volume by 88% vs the non-ultrasound Xe-ELIP group (64%). Behavioral tests mirrored neurological results.
Conclusions: One MHz continuous ultrasound can be used to release therapeutic gas from encapsulated liposomes. Administration of Xe-ELIP with ultrasound exposure over the carotid artery after a cerebral ischemic insult provides enhanced neuroprotection.
This research has received full or partial funding support from the American Heart Association, Midwest Affiliate (Illinois, Indiana, Iowa, Kansas, Michigan, Minnesota, Missouri, Nebraska, North Dakota, South Dakota & Wisconsin).