Domoic acid preconditioning and seizure induction in young and aged rats.

Domoic acid preconditioning and seizure induction in young and aged rats. Research Abstract Details 

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Domoic acid preconditioning and seizure induction in young and aged rats. Abstract Text:

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

Clinical reports suggest that the elderly are hypersensitive to the neurological effects of domoic acid (DOM). In the present study we assessed DOM-induced seizures in young and aged rats, and seizure attenuation following low-dose DOM pretreatment (i.e. preconditioning). Seizure behaviours following saline or DOM administration (0.5-2mg/kg i.p.) were continuously monitored for 2.5h in naïve and DOM preconditioned rats. Competitive ELISA was used to determine serum and brain DOM concentrations. Dose- and age-dependent increases in seizure activity were evident in response to DOM. Lower doses of DOM in young and aged rats promoted low level seizure behaviours. Animals administered high doses (2mg/kg in young; 1mg/kg in aged) progressed through various stages of stereotypical behaviour (e.g., head tics, scratching, wet dog shakes) before ultimately exhibiting tonic-clonic convulsions. Serum and brain DOM analysis indicated impaired renal clearance as contributory to increased DOM sensitivity in aged animals, and this was supported by seizure analysis following direct intrahippocampal administration of DOM. Preconditioning young and aged animals with low-dose DOM 45-90 min before high-dose DOM significantly reduced seizure intensity. We conclude that age-related supersensitivity to DOM is related to reduced clearance rather than increased neuronal sensitivity, and that preconditioning mechanisms underlying an inducible tolerance to excitotoxins are robustly expressed in both young and aged CNS.

Domoic acid preconditioning and seizure induction in young and aged rats. Publishing Authors By Initials

BR Hesp,AN Clarkson,PM Sawant,DS Kerr,

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Domoic acid preconditioning and seizure induction in young and aged rats. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Epilepsy research

VOLUME: 76

Page Numbers: 103-12

Journal Abbreviation: Epilepsy Res.

ISSN: 0920-1211

DAY: 22

MONTH: 08

YEAR: 2007

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LANGUAGE: eng

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Grant and Affiliation Information for Domoic acid preconditioning and seizure induction in young and aged rats.

AFFILIATION: Department of Pharmacology & Toxicology, University of Otago School of Medical Sciences, Dunedin, New Zealand.

Country: Netherlands

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MEDLINETA: Epilepsy Res

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