title: Role of endothelial nitric oxide synthase in cerebral blood flow changes during kainate seizures: a genetic approach using knockout mice.
abstract: The role of endothelial nitric oxide (NO) in the cerebrovascular response to partial seizures was investigated in mice deleted for the endothelial NO synthase gene (eNOS-/-) and in their paired wild-type (WT) congeners. Local cerebral blood flow (LCBF, quantitative [14C]iodoantipyrine method) was measured 3-6 h after unilateral kainate (KA) injection in the dorsal hippocampus; controls received saline. In WT mice, KA seizures induced a 22 to 50% LCBF increase restricted to the ipsilateral hippocampus, while significant LCBF decreases (15-33%) were noticed in 22% of the contralateral areas, i.e., the parietal cortex, amygdala and three basal ganglia areas, compared to saline-injected WT mice. In eNOS-/- mice, no LCBF increases were recorded within the epileptic focus and generalized contralateral LCBF decreases (22-46%) were noticed in 2/3 of the brain areas, compared to saline-injected eNOS-/- mice. Thus, endothelial NO is the mediator of the cerebrovascular response within the epileptic focus and participates in the maintenance of LCBF in distant areas.
authors.affiliation: INSERM U 398, Faculté de Médecine, 11 rue Humann, 67085 Strasbourg Cédex, France. Pereira@neurochem.u-strasbg.fr
authors.forename: Anne
authors.initials: A
authors.lastname: Pereira de Vasconcelos
authors.forename: Véronique
authors.initials: V
authors.lastname: Riban
authors.forename: Claude
authors.initials: C
authors.lastname: Wasterlain
authors.forename: Astrid
authors.initials: A
authors.lastname: Nehlig
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply* / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D018690:Excitatory Amino Acid Agonists / Q000008:administration & dosage; D007276:Injections, Intraventricular; D007608:Kainic Acid / Q000008:administration & dosage; D051379:Mice; D018345:Mice, Knockout; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000172:deficiency* / Q000235:genetics; D012640:Seizures / Q000139:chemically induced / Q000201:enzymology*
chemical_list: D018690:Excitatory Amino Acid Agonists; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; D007608:Kainic Acid