Perinatal brain injury impacts on motor and cognitive development, muscle structure, and gut composition, with functional improvement following gut-targeted interventions

Perinatal ischemic stroke is an early developmental brain injury caused by the obstruction of cerebral blood vessels. It is the leading cause of cerebral palsy and cognitive disabilities in survivors, and progress in unraveling its impact on the brain and other systems, aka the development of new effective therapies, has been limited, in part due to the scarcity of preclinical models. Here, we induced ischemic stroke in mice at perinatal age, and we studied the impact in and outside the brain across development till adulthood. We found that perinatal stroke disrupted fine motor development till adulthood and impaired memory. Moreover, perinatal stroke induced structural alterations in the skeletal muscle structure alongside significant shifts in gut microbiota composition. Notably, gut‑targeted intervention by fecal microbiota transplantation improved fine motor functions. Our findings showed for the first time the impact of the perinatal stroke on motor and cognitive across development, it reveals its effects beyond the brain, and identifies gut microbiota modulation as a safe and promising strategy to improve motor outcomes after stroke.