Background and objectives: Cerebral Palsy (CP) is a neurodevelopmental disorder characterized by motor and cognitive impairments resulting from early brain injury. Sensorimotor stimulation during critical developmental periods has been shown to mitigate brain damage and motor dysfunction. Since corticospinal tract (CST) undergoes crucial organization within the first two years of life, this period may represent a potential window for early interventions to promote CST reorganization and accelerate musculoskeletal recovery. In this study, we investigated whether early-life swimming (SWIM) could prevent the establishment of CP-related motor deficits and brain function alterations in a rodent model of CP. We hypothesize this rehabilitation will benefit from the higher brain plasticity at early stages to improve function. Moreover, we investigated possible molecular mechanisms underlying swimming- induced potential neuroprotection.
Methods: Pregnant Wistar rats were administered lipopolysaccharide (LPS, 200 mg/kg IP) on embryonic days 18 and 19. At postnatal day 0 (P0), pups underwent a 20-minute anoxia exposure (37°C). From P2 to P21, animals underwent hindlimb movement restriction for 16 hours / day. Additionally, from P8 to P21, self-initiated repetitive movements were induced through swimming (SWIM) in 32±1°C water, starting at 5 minutes per session and progressively increasing to 30 minutes. Functional ultrasound (fUS), 3D kinematic gait analysis, and rotarod test were conducted at P29. Key mediators of muscle-brain communication involved in neuroplasticity and motor recovery were assessed by western blot and RT-qPCR (FNDC5/irisin, BDNF, synaptophysin, SOX2) at P29 in gastrocnemius hindlimb muscle and hippocampus.
Results: CP resulted in reduced weight gain, with no detrimental or beneficial effects of swimming. CP led to decreased muscle mass in gastrocnemius muscles, with no improvement following swimming intervention. Increased brain connectivity was observed in CP animals, with limited modulation by swimming. However, gross motor function was improved in CP animals following SWIM, and locomotor performance was enhanced in female CP-SWIM animals specifically. FNDC5 was slightly increased in the gastrocnemius muscle of CP rats and SWIM had limited effect on this pathway. Also, a trend to increase SOX2 mRNA level due to swimming was observed, which could indicate increased hippocampal neurogenesis.
Conclusion: While early-life swimming did not mitigate CP-induced muscle atrophy or weight loss, it showed potential in improving brain connectivity, gross motor function and locomotion. These findings highlight the need for further investigation of the mechanisms underlying locomotor improvements following early-life interventions.
