Abstract WP355: Timing-Dependent Effects of Choline Supplementation on Post-Stroke Cognitive Recovery in Mice

Introduction: The cholinergic anti-inflammatory pathway, mediated by the alpha7 nicotinic acetylcholine receptor (alpha7nAChR), modulates immune responses and reduces inflammation. In young mice, αlpha7nAChR activation mitigates ischemic stroke injury by decreasing neuroinflammation and oxidative stress. However, the impact of timely alpha7nAChR stimulation on long-term cognitive outcomes remains understudied. We evaluated whether stimulation of alpha7nAChR via choline, a dietary agonist, could improve cognitive recovery after stroke. We hypothesized that choline supplementation would enhance post-stroke cognitive outcomes, with greater benefit when initiated immediately versus one month after stroke. Methods: Young (8–12 weeks) male wild-type mice underwent 60-min middle cerebral artery occlusion (MCAO) and were assigned to: (A) choline-supplemented diet (5 g/kg choline chloride) immediately post-stroke; (B) choline-supplemented diet starting 1-month post-stroke; or (C) control diet. Cognitive testing included Y-maze and Barnes maze (month 1), novel object recognition (month 2), and object location test (month 3). Results: At 1-month post-MCAO, percentage alternation did not differ among groups on Y maze. In the Barnes maze, control diet MCAO mice showed prolonged escape latency (p<0.0001 vs. sham), while immediate choline mice performed better than control diet (p=0.009). At 2 months after MCAO, immediate choline mice had a higher discrimination index in novel object recognition than control diet, with no difference between control diet and delayed choline was observed. At 3 months after MCAO, both immediate (p=0.0073) and delayed (p=0.0006) choline groups outperformed control diet in object location discrimination. Conclusion: Choline supplementation improves long-term cognitive outcomes after ischemic stroke in young mice, with earlier initiation providing greater benefit. These findings support αlpha7nAChR activation via dietary choline as a potential strategy to enhance post-stroke recovery.