Role of nitric oxide in cerebral blood flow changes during kainate seizures in mice: genetic and pharmacological approaches

Abstract

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 14C-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.

Keywords

• Neuronal nitric oxide synthase
• Knockout mice
• 7-Nitroindazole
• Kainate seizures
• Intrahippocampal injection
• Cerebral blood flow