Cuboni, G.; Campuzano, C.; Vignozzi, L.; Liotta, R.; Pinzauti, D.; Vitale, G.; Tonellato, M.; di Gesu, R.; Biazzo, M.; Rigoni, M.; Allegra, M.; Deidda, G.

Perinatal ischemic stroke is an early developmental brain injury caused by obstruction of cerebral blood vessels and is a leading cause of cerebral palsy and cognitive disability in survivors. However, progress in understanding its impact on the brain and other organ systems, as well as in developing effective therapies, remains limited, in part due to the scarcity of relevant preclinical models. Here, we induced ischemic stroke via middle cerebral artery occlusion in perinatal mice and investigated its effects within and beyond the brain across development into adulthood. We found that perinatal stroke disrupted fine motor development and impaired memory. In addition, it induced structural alterations in skeletal muscle and significant changes in gut microbiota composition. Notably, gut-targeted intervention using fecal microbiota transplantation improved fine motor function. Our findings demonstrate, for the first time, the multisystem developmental impact of perinatal stroke, extending beyond the brain, and identify gut microbiota modulation as a promising and potentially safe therapeutic strategy to improve motor outcomes after stroke.