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Introduction/Purpose Intracranial aneurysms (IAs) are dilated regions of cerebral arterial wall that are vulnerable to rupture, causing significant morbidity and mortality. Flow-diverting stents (FDSs) mitigate the risk of rupture but are limited by thrombogenicity and incomplete aneurysm occlusion. Adjunctive cell therapy is a viable strategy to address these limitations; however, cell immunogenicity remains a consideration, and often requires immunosuppression in preclinical models.Immunosuppression using agents such as cyclosporine A (CsA) is a significant confounding variable in preclinical experiments, but its effect remains poorly characterized in the context of FDS treatment. The current study aims to evaluate the impact of CsA on angiographic aneurysm occlusion following FDS treatment.Materials and Methods Saccular aneurysms were created in six female New Zealand White rabbits. All animals were treated with an FDS (Pipeline Embolization Device, Medtronic) and were allocated to control (n = 3) or CsA (n=3) groups. For each animal, angiography was collected at two- and four-weeks post-FDS deployment. Angiographic occlusion was scored by a blinded neurointerventionalist using the O’Kelly Marotta scale, with adequate occlusion defined as grade C or D.Following this, aneurysm sites were H&E stained, and aneurysm and parent vessel characteristics were scored by a blinded histopathologist using a series of five-point scales. Between-group comparisons were performed using the Mann-Whitney U test, with an α of 0.10.Results Two-week angiographic occlusion was comparable between groups (p = 0.32). At four weeks, adequate occlusion was achieved in 3/3 control animals and 1/3 CsA treated animals ( figure 1; p = 0.07). Histological analysis found comparable endothelialization of the stent between groups; however, analysis of the aneurysm sac suggested a trend toward more organized intrasaccular thrombus in the control group (scores 3-4) compared to the CsA group (scores 0-2; p = 0.2).Conclusions The results of the current study suggest that CsA administration may negatively impact angiographic occlusion, potentially via inhibition of intra-aneurysmal thrombus organization. These findings highlight the need for further investigation of the impact of CsA on thrombus organization, as such effects have important implications for the design of preclinical studies and clinical translatability.Disclosures P. Croney: None. M. Eesa: 4; C; Fluid Biomed Inc. A. Bromley: None. M. Badv: None. A. Mitha: 2; C; Stryker, Microvention. 4; C; Fluid Biomed Inc.Abstract O-039 Figure 1