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