Role of the calcium plateau in neuronal injury and behavioral morbidities following organophosphate intoxication

Ann N Y Acad Sci. 2016 Jun;1374(1):176-83. doi: 10.1111/nyas.13122. Epub 2016 Jun 21.


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.

Keywords: calcium; carisbamate; cell death; dantrolene; paraoxon; status epilepticus.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Behavior, Animal / drug effects*
  • Calcium / metabolism*
  • Disease Models, Animal
  • Humans
  • Neurons / drug effects
  • Neurons / metabolism
  • Neurons / pathology*
  • Organophosphorus Compounds / toxicity*
  • Risk Factors
  • Status Epilepticus / chemically induced
  • Status Epilepticus / pathology


  • Organophosphorus Compounds
  • Calcium