Phosphate energy metabolism during domoic acid-induced seizures

The effect of domoic acid-induced seizure activity on energy metabolism and on brain pH in mice was studied by continuous EEG recording and in vivo 31P nuclear magnetic resonance (NMR) spectroscopy. Mice were divided into ventilated (n = 6) and nonventilated (n = 7) groups. Baseline EEG was 0.1-mV amplitude with frequence of > 30-Hz and of 4-5 Hz. After intraperitoneal (i.p.) administration of domoic acid (6 mg/kg), electrographic spikes appeared at increasing frequency, progressing to high-amplitude (0.1-0.8 mV) continuous seizure activity (status epilepticus). In ventilated mice, the [31P]NMR spectra showed that high-energy phosphate levels and tissue pH did not change after domoic acid administration or during the intervals of spiking or status epilepticus. Nonventilated mice showed periods of EEG suppression accompanied by decreases in the levels of high-energy phosphate metabolites and in pH, corresponding to episodic respiratory suppression during the spiking interval. In all animals, status epilepticus was followed by a marked decrease in EEG amplitude that progressed rapidly to isoelectric silence. [31P]NMR spectra obtained after this were indicative of total energy failure and tissue acidosis. In a separate group of ventilated mice (n = 4), domoic acid-induced status epilepticus was accompanied initially by an increase in mean arterial blood pressure (MAP) that slowly returned to baseline level. Isoelectric silence was accompanied by a decrease in MAP to 75 +/- 8 mm Hg. These experiments suggest that domoic acid-induced seizures are not accompanied by an increase in substrate demand that exceeds supply.