Document Type

Article

Original Publication Date

2016

Journal/Book/Conference Title

Annals of the New York Academy of Sciences

Volume

1374

First Page

176

Last Page

183

DOI of Original Publication

10.1111/nyas.13122

Comments

Originally published at http://doi.org/10.1111/nyas.13122

Date of Submission

October 2016

Abstract

Organophosphate (OP) chemicals include nerve agents and pesticides, and there is a growing concern of OP based chemical attacks against civilians. Current antidotes are essential in limiting immediate mortality associated with OP exposure. However, further research is needed to identify molecular mechanisms underlying long-term neurological deficits following survival of OP toxicity in order to develop effective therapeutics. We have developed rat survival models of OP induced status epilepticus (SE) that mimic chronic mortality and morbidity following OP intoxication. We have observed significant elevations in hippocampal calcium levels after OP SE that persisted for weeks following initial survival. Drugs inhibiting intracellular calcium-induced calcium release such as dantrolene, levetiracetam, and carisbamate lowered OP-SE mediated protracted calcium elevations. Given the critical role of calcium signaling in modulating behavior and cell-death mechanisms, drugs targeted at preventing the development of the calcium plateau could enhance neuroprotection, help reduce morbidity and improve outcome following survival of OP SE.

Rights

© 2016 New York Academy of Sciences.

Is Part Of

VCU Neurology Publications

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