Spectral analysis of electrocorticographic activity during pharmacological preconditioning and seizure induction by intrahippocampal domoic acid

Abstract

Previously we have shown that low-dose domoic acid (DA) preconditioning produces tolerance to the behavioral effects of high-dose DA. In this study, we used electrocorticography (ECoG) to monitor subtle CNS changes during and after preconditioning. Young adult male Sprague-Dawley rats were implanted with a left cortical electrode, and acute recordings were obtained during preconditioning by contralateral intrahippocampal administration of either low-dose DA (15 pmoles) or saline, followed by a high-dose DA (100 pmoles) challenge. ECoG data were analyzed by fast Fourier transformation to obtain the percentage of baseline power spectral density (PSD) for delta to gamma frequencies (range: 1.25-100 Hz). Consistent with previous results, behavioral analysis confirmed that low-dose DA preconditioning 60 min before a high-dose DA challenge produced significant reductions in cumulative seizure scores and high level seizure behaviors. ECoG analysis revealed significant reductions in power spectral density across all frequency bands, and high-frequency/high-amplitude spiking in DA preconditioned animals, relative to saline controls. Significant correlations between seizure scores and ECoG power confirmed that behavioral analysis is a reliable marker for seizure analysis. The reduction of power in delta to gamma frequency bands in contralateral cortex does not allow a clear distinction between seizure initiation and seizure propagation, but does provide objective confirmation that pharmacological preconditioning by DA reduces network seizure activity.

Ischemic Cardiomyopathy Following Seizure Induction by Domoic Acid

“…Immediately after drug administration, the animals were returned to the observation chamber and their behaviors were observed for 2 hours in a cycle of 1 minute on and 4 minutes off, with all behavioral responses during each observation period coded and logged electronically, as described previously. 8,11,13 Behaviors were rated using a modified version of the seizure scale: level 0, normal resting or exploratory behaviors; level 1, discomfort behaviors; level 2, stereotypical behaviors confined to the head and neck region; level 3, moderate seizure behaviors associated with stereotypical movements of the limbs or trunk; and level 4, severe generalized seizure behaviors, with level 4 leading to level 5, clonic-tonic convulsions. Animals experiencing more than two periods of prolonged clonictonic convulsions were immediately sacrificed in compliance with ethical requirements and all subsequent observation periods were logged as level 5.…”

“…1 As a consequence of heightened interest in the mechanism of DOM toxicity, a number of experimental studies have investigated the consequences of DOM exposure on behavioral and neurological responses in laboratory animals. 4,[7][8][9][10][11][12][13] Within neuronal tissue, DOM has been shown to activate ␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainic acid (KA) receptors and results in the release of glutamate. 14 Overstimulation of ionotropic glutamate receptors (iGluR), namely N-methyl-D-aspartate (NMDA) receptors, provokes pathophysiological increases in intracellular Ca 2ϩ and consequently leads to the activation of several overlapping Ca 2ϩ -dependent processes, such as the generation of mitochondrial reactive oxygen species and loss of cellular viability.…”

Cardiac electrographic and morphological changes following status epilepticus: Effect of clonidine

“…11 Excitotoxic seizure induction with KA in rat models produces escalating levels of behavioural responses which include head tremors, wet dog shakes (WDS) and eventually clonic-tonic convulsions. 12,13 Previous studies by our group demonstrated that neither KA nor domoic acid produce direct toxic effects on rat cardiomyocyte or isolated heart preparations. 14 Furthermore, we have shown that domoic acid-induced SE produces identical patterns of structural cardiomyopathy, irrespective of whether the excitotoxin is delivered through central or systemic routes.…”

Troxerutin Counteracts Domoic Acid–Induced Memory Deficits in Mice by Inhibiting CCAAT/Enhancer Binding Protein β–Mediated Inflammatory Response and Oxidative Stress

“…D omoic acid (DA), a naturally occurring marine neurotoxin produced by members of the diatom genus Pseudonitzschia, has been reported to be a structural relative to kainic acid (KA) and can induce neuronal excitotoxicity via activation of aminopropionic acid and KA receptors (1)(2)(3)(4). Several lines of evidence show that activation of KA receptors impairs mitochondrial function, provokes the release of inflammatory factors, and increases the generation of reactive oxygen species (ROS), which disrupt neural signaling pathways and cause structural cellular damage, ultimately leading to cognitive deficits and brain damage (2,(5)(6)(7)(8)(9)(10).…”