Federal Grant Award Summary

The National Institute of Neurological Disorders and Stroke (NINDS) awarded Massachusetts General Hospital a Project Grant in the amount of $648,672 on June 11, 2026, under the Extramural Research Programs in the Neurosciences and Neurological Disorders (CFDA 93.853) program. This translational research initiative, extending through March 31, 2031, investigates circadian regulation mechanisms that influence the efficacy of reperfusion therapy in acute ischemic stroke patients. The research employs an integrated multi-principal investigator approach combining clinical neuroimaging analysis, biomarker evaluation, mouse stroke models, and molecular pharmacology to determine whether circadian timing affects patient responsiveness to mechanical thrombectomy and whether targeting circadian mechanisms could improve treatment outcomes for non-responsive patients.

The project delivers three coordinated research aims: neuroimaging analysis demonstrating that morning strokes present less severe tissue injury patterns and better reperfusion response; clinical biomarker correlation studies showing that circadian-dependent endothelial dysfunction, dampened vasodilation, and increased immunothrombotic activity characterize non-responsive cases; and preclinical and pharmacological validation through mouse models and molecular interventions targeting circadian pathways. This research addresses a significant gap in stroke treatment by exploring why patients with large ischemic cores may still benefit from reperfusion therapy, with potential implications for identifying optimal treatment candidates and developing circadian-informed therapeutic strategies.