Abstract 4146671: Validation of Xenon (Xe)-Liposomal Cerebroprotection for Ischemic Stroke

Background: Xe-liposome therapy has shown cerebroprotection in adult stroke animals. This study aims to validate the Xe therapeutic effect by MRI in adult rats and the therapeutic effect in an aged animal. Method: A 2-hour MCAO was induced in adult rodents. The MCAO animals were then divided into two groups: one receiving no treatment and the other receiving Xe-liposomal treatment (3 doses within 2-6 hours after stroke followed by 1 dose per day). Diffusion-weighted MRI conducted at 2, 6, and 24 hours post-MCAO, were analyzed by our image center. For aged rats (14 rats, 74 weeks old, male and female), MCAO (1.5 hours) was induced and then divided into two groups: stroke without treatment (n=5) and stroke with Xe-liposome treatment (n=9) and given 3 doses at day one and once per day for following days. Neurological function was tested by Limb placement and rotarod, and infarct volumes were measured two days post-stroke/treatment. Results: MRI (Fig.) demonstrated that infarct volume growth ratio was lower in the Xe-treated animals than those without treatment, indicating a protective effect of Xe against ischemic injury. MCAO induced 25% ± 5.4% infarct volume in the aged animals. Xe- reduced the infarct size to 6.7% ± 3.4%. Xe treatment demonstrated improved neurological functional recovery in these aged stroke animals. Conclusions: Xe-liposomal treatment reduces ischemic core growth in adult rats and has a therapeutic effect in aged stroke animals. These results support further development of Xe-based therapies for stroke.