Objectives and design: The present investigation examines the effects of increasing central nervous system (CNS) levels of nitric oxide (NO), via the administration of L-arginine, on the development of experimental allergic encephalomyelitis (EAE).
Subjects: EAE was induced in male Lewis rats (200-250 g).
Treatment: Normal rats were orally dosed with L-arginine (300 mg/kg body weight) once daily for 12 days. EAE-sensitised animals received L-arginine (300 mg/kg body weight) once daily from day 1 to 12 post-inoculation.
Methods: Neurological and histological development of EAE were assessed. In addition, CNS cytosol levels of nitrite, superoxide and hydrogen peroxide were measured. Results were analysed using the Mann Whitney U-test and Chi-squared test.
Results: L-arginine administration significantly delayed disease onset (p < 0.05) and reduced the severity of neurological (p < 0.05) and histological (p < 0.001) signs of EAE. Treatment with L-arginine caused a significant elevation in CNS nitrite concentrations (p < 0.05) which in EAE-sensitised animals was associated with a concomitant and dramatic decrease in superoxide (p < 0.05) and hydrogen peroxide (p < 0.05) levels.
Conclusions: The results suggest that NO may act as a protective molecule during the development of EAE possibly via the modulation of oxidant-mediated neuroinflammation.