Domoic acid induced seizures progress to a chronic state of epilepsy in rats

Adverse Outcome Pathway on binding of agonists to ionotropic glutamate receptors in adult brain leading to excitotoxicity that mediates neuronal cell death, contributing to learning and memory impairment

“…Similar effects were observed in other in vivio studies (Fuquay et al, 2012;Muha and Ramsdell, 2011). …”

Magnetic resonance imaging reveals that brain atrophy is more severe in older California sea lions with domoic acid toxicosis

“…In rats, it has been shown that only a single exposure to DA is sufficient to develop spontaneous recurrent seizures (SRS) within six months (Muha and Ramsdell, 2011). These findings suggest that DA can lead to a nonlethal status epilepticus, which can progress to epilepsy (Muha and Ramsdell, 2011).…”

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

“…Two groups of 6 late juvenile (7 week) male rats (5 treated with domoic acid and one with PBS vehicle) were subject to an established protocol developed for kainic acid (Hellier and Dudek 2005) and modified for domoic acid (Muha and Ramsdell 2011) to induce a nonlethal SE that develops over weeks to chronic spontaneous recurrent seizures. Male rats were chosen because the estrous cycle has been reported to add variance in the kainic acid dosing protocol to induce a nonlethal SE (Hellier and Dudek 2005).…”

“…To combat lethality, doses were lowered or administered in the presence of agents to control seizures, but failed to lead to long-term epileptic behavior (Perez-Mendes et al 2005). Muha and Ramsdell (2011) used a modified dosing triturated protocol, similar to an established kindling protocol with the related experimental drug kainic acid, in rats to model aspects of human temporal lobe epilepsy (Hellier and Dudek 2005). This model accurately replicated a domoic acid-nduced SE that successfully leads to a chronic state of recurrent spontaneous seizures weeks to months later (Muha and Ramsdell 2011) and atypical aggressive behavior (Fuquay et al 2012).…”