DUAL INTERVENTION OF NO IN EXPERIMENTAL A FRICAN TRYPANOSOMIASIS

Patients with human African trypanosomiasis present a major dysruption of the circadian rhythmicity of the sleep-wake cycle, which war also found in rats infected with Trypanosoma brucei brucei (T.b.b.). The al terations in the immune function and nervous system in African trypsan osomiasis led us to investigate the involvement of nitric oxide (NO), a key molecule in immune and neurophysiological mechanisms, in experim ental trypanosomiasis. NO was measured in 35 Sprague Dawley rats using differential impulsional voltammetry with a carbon fiber roared with porphyrin-nickel and nafion, ex vivo in the blood and in vivo in the b rain. The rats were anaesthetized with sodium chlorate. Infection was performed intraperitoneally (i.p.) with 0.2 ml of a T.b.b. cryostabila te (clone An rat 1.1E). Blood was collected by an intracardiac punctur e with immediate replacement of blood volume (1 ml) in 7 control rats and 8 rats infected since 15 days, before and after i.p. administratio n of L-ANA (L-arginine-p-nitro-anilide, 100 mg.kg(-1), an inhibitor of NO synthase). Brain measures were done in 20 rats (8 controls, and 12 rats infected since 15 or 21 days), in the cortex (H, -0.5 mm; AP -0. 8 mm; L, 1.2 mm) and the lateral ventricle (H, 3.2 mm). In infected ra ts, blood NO was at 70% of control values (p < 0.001, and L-ANA suppre ssed the NO signal in all animals (p < 0.0001), demonstrating that the signal originated from NO. Cortical NO was higher than in the ventric le in both control (p < 0.0001) and infected rats (p < 0.001). NO was more elevated in both structures in 15-day-infected rats than in contr ol rats (p < 0.0001), the difference being enhanced in 21-day-infected rats (P < 0.001). L-ANA suppressed the NO signal in 30 to 60 min. The se data suggest that NO intervenes in the development of trypanosomias is in different manners. It is increased in the brain, which remains u nexplained where it may be involved in blood-brain barrier permeation. Conversely, it is decreased in the blood, may be because of macrophag e function impairment which would explain why trypanosomes can multipl y in the host.