Abstract 3499: Novel Nitric Oxide-Containing Echogenic Liposome for the Treatment of Vasospasm Following Subarachnoid Hemorrhage

Background: Cerebral vasospasm following aneurysmal subarachnoid hemorrhage (SAH) is a major cause of high morbidity and mortality. The reduced availability of nitric oxide (NO) in blood and cerebrospinal fluid (CSF) is suggested an important mechanism underlying cerebral vasospasm, a complication of SAH. NO or NO donors are known to have potent effects on cerebral vascular relaxation. We have developed NO-containing echogenic liposomes (NO-ELIP) for NO delivery to assess the role of NO in SAH-induced vasospasm. We hypothesized that NO-ELIP can produce vasodilation and provide an effective therapeutic approach to treat vasospasm following SAH. Methods: NO-ELIP was created by a freeze-under-pressure method. Male Sprague- Dawley rats (n=9) underwent SAH by puncturing the right middle cerebral artery with a sharp tip nylon monofilament. In the treatment groups, NO-ELIP were administered through the right femoral vein at 24 hours after SAH onset. The brain tissue was obtained for H&E staining at 30 min after NO-ELIP administration. Measurement of the posterior communicating artery was performed to evaluate the effects of NO-ELIP treatment on vasospasm following SAH. Results: After SAH, the normalized lumenal and wall thickness areas decreased from 1.02 ± 0.08 to 0.40 ± 0.15 (p Conclusion: This study demonstrates that NO-ELIP have the potential to deliver NO for therapeutic treatment of vasospasm. Enhancing the release of NO from circulating NO-ELIP by combining ultrasound exposure over the carotid artery may further provide an improved treatment strategy. This suggests that targeted therapeutic gas can be delivered to the cerebral circulation for the treatment of vasospasm following SAH