Very early swimming prevents the establishment of musculoskeletal dysfunction in a rodent model of Cerebral Palsy

Cerebral palsy (CP) is characterized by motor and cognitive impairments resulting from injuries to the central nervous system. Targeting early muscle activity during critical developmental periods may prevent musculoskeletal damage associated with CP through muscle-derived antioxidant and trophic factors released upon activation. We investigated whether early-life swimming (SW) prevents the establishment of musculoskeletal deficits in a CP rat model. Pregnant Wistar rats received intraperitoneal injections of lipopolysaccharide (LPS; 200mg/kg) on embryonic days 18 and 19. At birth (P0), CP pups were subjected to 20minutes of anoxia (37°C) and underwent hindlimbs movement restriction from P2 to P21 (16h/day). From P7 to P21, animals performed daily swimming sessions (from 5 to a maximum of 30minutes/day) in a tank filled with water (32°C). Locomotor function was assessed using Rota-rod and open field; H-reflex excitability, spinal cord tissue and gastrocnemius muscles were collected at P29 for biochemical and histological analyses. Early SW improved gross motor abilities in CP animals without major effects on exploratory drive. Although SW did not rescue CP-induced sarcopenia in soleus/gastrocnemius muscles, it significantly attenuated hyperreflexia and prevented spinal cord impairments in synaptic markers induced by the model. CP increased the expression of oxidative stress-related genes in skeletal muscle. Swimming favored more mature-like muscle architecture despite persistent muscle mass deficits and increased the mRNA expression of genes involved in antioxidant function and myokines. Early swimming mitigated key features of CP in rats and has high therapeutic potential when used in this critical developmental window.