EARLY LIFE SWIMMING AS A PREVENTIVE INTERVENTION IN A RODENT MODEL OF CEREBRAL PALSY

Cerebral Palsy (CP) is characterized by motor and cognitive impairments resulting from insults to the developing brain. Sensorimotor stimulation in the early developmental stages decrease brain damage and motor dysfunction. Since the corticospinal tract (CST) is organized during the first two years of life, this period may be a window of opportunity for optimizing interventions. We tested swimming (SW) during early life to prevent the establishment of the phenotype in a CP rodent model. Pregnant Wistar rats were injected with LPS (200mg/kg IP on E18 and E19). At P0, pups were exposed to anoxia for 20’ (37°C). From postnatal day 2 to 21, animals' hindlimbs movements were restricted for 16h/day. From P7 to P21, self-initiated repetitive movements induced by swimming were performed in water (32°C) starting from 5 minutes and constantly increasing 10'/day reaching 30’. Locomotor function and 3D kinematic gait analysis, H-reflex EMG and brain functional resting state connectivity were assessed at P28. Motor function was improved in CPSW group and gait dysfunction was preserved mainly in females. CP induced marked sarcopenia with no benefits of SW. However, SW improved the lack of frequency-dependent depression induced by CP. Brain hyper-connectivity induced by the model was reversed by SW and a protocol of hindlimbs stimulation evidenced cortico-thalamic disruption of brain connectivity in CP and reversed by SW. Swimming prevented locomotor deficits and improved gait kinematics, reversed musculoskeletal dysfunction and decreased brain hyperconnectivity induced by CP reinforcing the need for early diagnosis to optimize therapeutic benefits for CP population.