Role of endothelial nitric oxide synthase in cerebral blood flow changes during kainate seizures: a genetic approach using knockout mice.
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.
Pereira de Vasconcelos
Anne
A
INSERM U 398, Faculté de Médecine, 11 rue Humann, 67085 Strasbourg Cédex, France. Pereira@neurochem.u-strasbg.fr
Riban
Véronique
V
Wasterlain
Claude
C
Nehlig
Astrid
A
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*
D018690:Excitatory Amino Acid Agonists; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; D007608:Kainic Acid