Abstract 40: Xenon-Loaded Liposomes in Combination with IV tPA Extends the Time Window for Treatment of Thrombotic Stroke
BACKGROUND: Xenon (Xe) provides great promise for stroke treatment due to its unique neuroprotective effect. Building on previous work for Xe-loaded liposomes (Xe-ELIP) to effectively deliver Xe into the brain, this study investigates the effect of Xe-ELIP in combination with intravenously (IV) administered tissue plasminogen activator (tPA) to extend the time window of treatment for embolic stroke.
METHODS: Thrombotic strokes were induced in rats by injecting a standardized blood clot into the middle cerebral artery. In the treatment groups, Xe-ELIP (20mg/kg) and tPA (10mg/kg) were administrated IV at 2 and 4 hours, respectively, after the stroke onset. Continuous wave ultrasound (1 MHz, 50% duty cycle, 1 W/cm2) was applied over the common carotid artery during Xe-ELIP administration to trigger Xe release. Behavioral tests were conducted three days after stroke. Following sacrifice, brain sections were evaluated with triphenyltetrazolium chloride (TTC) and Tunel staining. Infarct size was presented as normalized infarct volume (%).
RESULTS: Thrombotic stroke without treatment exhibited the largest infarct size (18.98±2%); tPA treatment reduced the infarct size to 6.1±1% (p<0.001 vs. no treatment). Xe-ELIP in combination with tPA treatment further reduced the infarct size to 1.8±0.4% (p=0.032 vs. tPA treatment; Fig 1a) with lower hemorrhagic adverse effects, improved neurological function and reduced apoptosis (Fig 1b).
CONCLUSIONS: This study demonstrates that Xe-ELIP in combination with IV tPA provides improved therapeutic efficacy with reduced neuronal cell death and tPA-associated hemorrhagic side effects. These results have important implications for extending the time window of treatment of thrombotic stroke.
- © 2012 by American Heart Association, Inc.