title: Effects of nitric oxide on blood-brain barrier permeability in common carp (Cyprinus carpio L.).
abstract: OBJECTIVE
  To determine in vivo effects of nitric oxide (NO) on blood-brain barrier (BBB) permeability in common carp (Cyprinus carpio L.).
  
  
  METHODS
  148 carp. PROCEDURES Carp received glyceryl trinitrate (1 mg/kg) as an NO donor or received no treatment (control group). Nitrite and nitrate concentrations in carp sera were determined 0.25, 1, 3, 6, 8, 12, and 24 hours after treatment. In control and treatment groups, BBB permeability was analyzed by assessment of leakage of Evans blue dye into various brain areas at 6, 12, and 24 hours after glyceryl trinitrate treatment. Brain edema was determined by means of the wet-dry weight method and assessed with light microscopy on H&E-stained preparations of tissues obtained 6 and 24 hours after glyceryl trinitrate treatment.
  
  
  RESULTS
  Treatment with glyceryl trinitrate induced endogenous synthesis of NO, which was upregulated 6 and 8 hours after treatment. Increased NO synthesis was associated with increased permeability of the BBB, which developed 6 hours after treatment with the NO donor. Although the BBB became impermeable again by 12 hours after glycerol trinitrate treatment, brain edema still persisted 24 hours after treatment.
  
  
  CONCLUSIONS
  In this study, treatment with an NO donor caused reversible opening of the BBB and brain edema in common carp. An intact BBB is important to prevent influx of potentially harmful substances into the brain. This investigation highlighted the possibility of BBB disarrangement caused by NO, a substance found in the CNS of all vertebrates evaluated.
authors.forename: Sanja
authors.initials: S
authors.lastname: Kovacić
authors.forename: Lada
authors.initials: L
authors.lastname: Rumora
authors.forename: Emil
authors.initials: E
authors.lastname: Gjurcevic
authors.forename: Maja Šegvic
authors.initials: MŠ
authors.lastname: Klaric
authors.forename: Goran
authors.initials: G
authors.lastname: Ivkic
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000502:physiology; D001929:Brain Edema / Q000139:chemically induced; D002347:Carps / Q000502:physiology*; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D009573:Nitrites / Q000097:blood; D005996:Nitroglycerin / Q000008:administration & dosage / Q000494:pharmacology*; D010539:Permeability; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D009566:Nitrates; D009573:Nitrites; D014665:Vasodilator Agents; D009569:Nitric Oxide; D005996:Nitroglycerin