Role of nitric oxide in cerebral blood flow changes during kainate seizures in mice: genetic and pharmacological approaches.
The role of neuronal nitric oxide (NO) in the cerebrovascular response to partial seizures induced by intrahippocampal injection of kainate (KA) was investigated in mice deleted for the neuronal NO synthase gene (nNOS-/-) and in wild-type controls (WT). A second group of WT mice received the nNOS inhibitor, 7-nitroindazole (WT-7NI). Local cerebral blood flow (LCBF) was measured using the quantitative (14)C-iodoantipyrine method. Within the epileptic focus, all three groups of seizing mice (WT, WT-7NI, and nNOS-/-) showed significant 26-88% LCBF increases in ipsilateral hippocampus, compared to saline-injected mice. Contralaterally to the epileptic focus, KA seizures induced a 21-47% LCBF decreases in hippocampus and limbic cortex of WT mice and in most contralateral brain structures of nNOS-/- mice, while WT-7NI mice showed no contralateral CBF change. Neuronal NO appears to be not involved in the cerebrovascular response within the epileptic focus, but may rather have a role in the maintenance of distant LCBF regulation during seizures.
de Vasconcelos
Anne Pereira
AP
INSERM U 398, Faculté de Médecine, 67085 Strasbourg Cédex, France. Pereira@neurochem.u-strasbg.fr
Bouilleret
Viviane
V
Riban
Véronique
V
Wasterlain
Claude
C
Nehlig
Astrid
A
D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D002540:Cerebral Cortex / Q000378:metabolism / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000235:genetics*; D003292:Convulsants; D004195:Disease Models, Animal; D004569:Electroencephalography; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004827:Epilepsy / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D007839:Functional Laterality / Q000235:genetics; D006624:Hippocampus / Q000378:metabolism / Q000503:physiopathology; D007191:Indazoles / Q000494:pharmacology; D007608:Kainic Acid; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000235:genetics*; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000235:genetics*; D052248:Nitric Oxide Synthase Type I; D013226:Status Epilepticus / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology
D003292:Convulsants; D004791:Enzyme Inhibitors; D007191:Indazoles; D009419:Nerve Tissue Proteins; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse; D007608:Kainic Acid; D000983:Antipyrine; C080122:7-nitroindazole; C008135:iodoantipyrine