Differential effects of physical exercise and L-arginine on cortical spreading depression in developing rats

Objective: We investigated the effect of early-in-life administration of L-arginine, combined with physical exercise, on cortical spreading depression (CSD) in young and adult rats. Methods: L-arginine (300 mg/kg/day, n = 40) or distilled water (vehicle, n = 40) was given to the rats during postnatal days 7-35 by gavage. Physical exercise (treadmill) was carried out during postnatal days 15-35 in half of the animals in each gavage condition described above. The other half (non-exercised) was used for comparison. When the animals reached 35-45 days (young groups) or 90-120 days of age (adult) CSD was recorded on two cortical points during 4 hours and CSD propagation velocity was calculated. Results: L-arginine-treated + exercised rats had increased body weight, but not brain weight, in adult age compared to L-arginine + non-exercised ones (P < 0.05). In both young and adult animals, L-arginine increased, whereas exercise decreased the CSD propagation velocity. Analysis of variance revealed a significant interaction between gavage treatment and age (P < 0.001), and also between gavage treatment and exercise (P = 0.004), but not between age and exercise. An additional control group of young rats, treated with 300 mg/kg of L-histidine, presented CSD velocities comparable to the corresponding water-treated controls, suggesting that the CSD acceleration seen in the L-arginine group was an L-arginine-specific effect, rather than an effect due to a non-specific amino acid imbalance. Discussion: L-arginine and exercise affect CSD differentially (L-arginine accelerated, while exercise decelerated CSD), and both effects did interact. Probably, they depend on developmental plasticity changes associated with the treatments.