title: Cerebral and peripheral changes occurring in nitric oxide (NO) synthesis in a rat model of sleeping sickness: identification of brain iNOS expressing cells.
abstract: BACKGROUND
  The implication of nitric oxide (NO) in the development of human African trypanosomiasis (HAT) using an animal model, was examined. The manner by which the trypanocidal activity of NO is impaired in the periphery and in the brain of rats infected with Trypanosoma brucei brucei (T. b. brucei) was analyzed through: (i) the changes occurring in NO concentration in both peripheral (blood) and cerebral compartments; (ii) the activity of nNOS and iNOS enzymes; (iii) identification of the brain cell types in which the NO-pathways are particularly active during the time-course of the infection.
  
  
  RESULTS
  NO concentration (direct measures by voltammetry) was determined in central (brain) and peripheral (blood) compartments in healthy and infected animals at various days post-infection: D5, D10, D16 and D22. Opposite changes were observed in the two compartments. NO production increased in the brain (hypothalamus) from D10 (+32%) to D16 (+71%), but decreased in the blood from D10 (-22%) to D16 (-46%) and D22 (-60%). In parallel with NO measures, cerebral iNOS activity increased and peaked significantly at D16 (up to +700%). However, nNOS activity did not vary. Immunohistochemical staining confirmed iNOS activation in several brain regions, particularly in the hypothalamus. In peritoneal macrophages, iNOS activity decreased from D10 (-83%) to D16 (-65%) and D22 (-74%) similarly to circulating NO.
  
  
  CONCLUSIONS
  The NO changes observed in our rat model were dependent on iNOS activity in both peripheral and central compartments. In the periphery, the NO production decrease may reflect an arginase-mediated synthesis of polyamines necessary to trypanosome growth. In the brain, the increased NO concentration may result from an enhanced activity of iNOS present in neurons and glial cells. It may be regarded as a marker of deleterious inflammatory reactions.
authors.affiliation: University of Lyon, Faculty of Medicine, EA 4170 Laboratory of Free Radicals, Energy Substrates and Cerebral Physiopathology, & Neurochem platform, Lyon, France.
authors.forename: Donia
authors.initials: D
authors.lastname: Amrouni
authors.forename: Sabine
authors.initials: S
authors.lastname: Gautier-Sauvigné
authors.forename: Anne
authors.initials: A
authors.lastname: Meiller
authors.forename: Philippe
authors.initials: P
authors.lastname: Vincendeau
authors.forename: Bernard
authors.initials: B
authors.lastname: Bouteille
authors.forename: Alain
authors.initials: A
authors.lastname: Buguet
authors.forename: Raymond
authors.initials: R
authors.lastname: Cespuglio
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000201:enzymology; D001921:Brain / Q000378:metabolism* / Q000469:parasitology / Q000473:pathology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D055664:Electrochemical Techniques; D004789:Enzyme Activation; D005455:Fluorescent Antibody Technique; D006790:Host-Parasite Interactions; D006801:Humans; D007150:Immunohistochemistry; D017737:Macrophages, Peritoneal / Q000201:enzymology; D008297:Male; D017628:Microglia / Q000201:enzymology; D009474:Neurons / Q000201:enzymology; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000097:blood; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014346:Trypanosoma brucei brucei / Q000502:physiology; D014353:Trypanosomiasis, African / Q000201:enzymology / Q000378:metabolism* / Q000469:parasitology
chemical_list: D009569:Nitric Oxide; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II