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Role of the calcium plateau in neuronal injury and behavioral morbidities following organophosphate intoxication
Author(s) -
Deshpande Laxmikant S.,
Blair Robert E.,
Phillips Kristin F.,
DeLorenzo Robert J.
Publication year - 2016
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/nyas.13122
Subject(s) - status epilepticus , organophosphate , calcium , neuroprotection , medicine , pharmacology , calcium in biology , levetiracetam , organophosphate poisoning , anesthesia , epilepsy , biology , pesticide , psychiatry , agronomy
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 the 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 outcomes following survival of OP SE.