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A Cupric Silver Histochemical Analysis of Domoic Acid Damage to Olfactory Pathways Following Status Epilepticus in a Rat Model for Chronic Recurrent Spontaneous Seizures and Aggressive Behavior

Author(s): Tiedeken, J.A.; N. Muha; J.S. Ramsdell.


Publication Type: Journal Article

Journal Title: Toxicologic Pathology

Date of Publication: 2013

Reference Information: 41(3): 454-469

Keywords: domoic acid; seizure; epilepsy; neurodegeneration; olfactory; rat; sea lion

Abstract: The amnesic shellfish toxin, domoic acid, interferes with glutamatergic pathways leading to neuronal damage, most notably causing memory loss and seizures. In this study, the authors utilized a recently developed rat model for domoic acid-induced epilepsy, an emerging disease appearing in California sea lions weeks to months after poisoning, to identify structural damage that may lead to a permanent epileptic state. Sprague Dawley rats were kindled with several low hourly intraperitoneal doses of domoic acid until a state of status epilepticus (SE) appears. This kindling approach has previously been shown to induce a permanent state of epileptic disease in 96% animals within 6 months. Three animals were selected for neurohistology a week after the initial SE. An amino cupric silver staining method using neutral red counterstain was used on every eighth 40 mm coronal section, from each brain to highlight neural degeneration from the olfactory bulb through the brain stem. The most extensive damage was found in the olfactory bulb and related olfactory pathways, including the anterior/medial olfactory cortices, endopiriform nucleus, and entorhinal cortex. These findings indicate that damage to olfactory pathways is prominent in a rat model for domoic acid-induced chronic recurrent spontaneous seizures and aggressive behavior.