Domoic acid preconditioning and seizure induction in young and aged rats

Hesp, Blair; Clarkson, Andrew N.; Sawant, Punam M.; Kerr, D. Steven

doi:10.1016/j.eplepsyres.2007.07.003

Cited by 34 publications

(36 citation statements)

References 61 publications

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“…The DOM doses used here have reproducibly been shown by our group to elicit similar, moderately high seizure scores. 11,43 Seizure level scoring was performed for the first 2 hours immediately after drug or vehicle administration, as described below. Cumulative seizure score analysis, calculated as the sum of the highest individual scores recorded during the observation period, were used to produce excitotoxin intraperitoneally and intrahippocampally treated groups with similar seizure scores.…”

Section: Experimental Protocolmentioning

confidence: 99%

“…11 Animals receiving systemic DOM (intraperitoneally) were then randomly allocated into four subgroups (n ϭ 8/group) and were sacrificed at 1, 3, 7, and 14 days after DOM administration. Two age-and weight-matched intraperitoneally saline-treated animal control groups were included (n ϭ 5/group) and were sacrificed 1 and 14 days after saline administration.…”

Section: Intraperitoneal Dosingmentioning

confidence: 99%

“…11,43 Cannula implantation surgery was performed on the intrahippocampal study group 1 week before DOM or vehicle administration. Rats were pretreated with dihydrostreptomycin (250 IU, s.c.) and carprofen (4 mg/kg, s.c.), anesthetized with ketamine (70 mg/kg, s.c.) and medetomidine hydrochloride (0.3 mg/ kg, s.c.), and stereotactically (Narishige Scientific Instruments, Tokyo) implanted with a unilateral drug delivery cannula into the ventral hippocampus (using bregma as reference: 5.2 mm posterior, 5.0 mm lateral to the right, 5.2 mm depth from cranial surface).…”

Section: Intrahippocampal Dosingmentioning

confidence: 99%

“…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.…”

Section: Behavioral Analysis After Dom Administrationmentioning

confidence: 99%

“…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.…”

mentioning

confidence: 99%

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Ischemic Cardiomyopathy Following Seizure Induction by Domoic Acid

Vranyac-Tramoundanas

Harrison

Sawant

et al. 2011

The American Journal of Pathology

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Exposure to the excitotoxin domoic acid (DOM) has been shown to produce cardiac lesions in both clinical and animal studies. We have previously shown that DOM failed to directly affect cardiomyocyte viability and energetics, but the development of this cardiomyopathy has remained unexplained. The present study compared effects of high-level seizure induction obtained by intraperitoneal (2 mg/kg) or intrahippocampal (100 pmol) bolus administration of DOM on development of cardiac pathologies in a rat model. Assessment of cardiac pressure derivatives and coronary flow rates revealed a significant time-dependent decrease in combined left ventricular (LV) systolic and diastolic function at 1, 3, 7, and 14 days after intraperitoneal administration and at 7 and 14 days after intrahippocampal DOM administration. LV dysfunction was matched by a similar time-dependent decrease in mitochondrial respiratory control, associated with increased proton leakage, and in mitochondrial enzyme activities. Microscopic examination of the LV midplane revealed evidence of progressive multifocal ischemic damage within the subendocardial, septal, and papillary regions. Lesions ranged from reversible early damage (vacuolization) to hypercontracture and inflammatory necrosis progressing to fibrotic scarring. Plasma proinflammatory IL-1␣, IL-1␤, and TNF-␣ cytokine levels were also increased from 3 days after seizure induction. The observed cardiomyopathies did not differ between intraperitoneal and intrahippocampal groups, providing strong evidence that cardiac damage after DOM exposure is a consequence of a seizure-evoked autonomic response.

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Section: Experimental Protocolmentioning

confidence: 99%

Section: Intraperitoneal Dosingmentioning

confidence: 99%

Section: Intrahippocampal Dosingmentioning

confidence: 99%

Section: Behavioral Analysis After Dom Administrationmentioning

confidence: 99%

mentioning

confidence: 99%

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Ischemic Cardiomyopathy Following Seizure Induction by Domoic Acid

Vranyac-Tramoundanas

Harrison

Sawant

et al. 2011

The American Journal of Pathology

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

2010

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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.

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Domoic Acid As a Neurotoxin

Pérez-Gómez

Tasker

2021

Handbook of Neurotoxicity

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Domoic acid preconditioning and seizure induction in young and aged rats

Cited by 34 publications

References 61 publications

Ischemic Cardiomyopathy Following Seizure Induction by Domoic Acid

Ischemic Cardiomyopathy Following Seizure Induction by Domoic Acid

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

Domoic Acid As a Neurotoxin

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