Neuroinflammation as a Therapeutic Target for Mitigating the Long-Term Consequences of Acute Organophosphate Intoxication
Open Access
- 12 May 2021
- journal article
- review article
- Published by Frontiers Media SA in Frontiers in Pharmacology
Abstract
Acute intoxication with organophosphates (OPs) can cause a potentially fatal cholinergic crisis characterized by peripheral parasympathomimetic symptoms and seizures that rapidly progress to status epilepticus (SE). While current therapeutic countermeasures for acute OP intoxication significantly improve the chances of survival when administered promptly, they are insufficient for protecting individuals from chronic neurologic outcomes such as cognitive deficits, affective disorders, and acquired epilepsy. Neuroinflammation is posited to contribute to the pathogenesis of these long-term neurologic sequelae. In this review, we summarize what is currently known regarding the progression of neuroinflammatory responses after acute OP intoxication. We also discuss studies in which neuroinflammation was targeted following OP-induced SE, and explain possible reasons why such therapeutic interventions have inconsistently and only partially improved long-term outcomes. Finally, we suggest future directions for the development of therapeutic strategies that target neuroinflammation to mitigate the neurologic sequelae of acute OP intoxication.Funding Information
- National Institute of Neurological Disorders and Stroke
This publication has 157 references indexed in Scilit:
- A review of experimental evidence linking neurotoxic organophosphorus compounds and inflammationNeuroToxicology, 2012
- Small molecule antagonist reveals seizure-induced mediation of neuronal injury by prostaglandin E2 receptor subtype EP2Proceedings of the National Academy of Sciences of the United States of America, 2012
- Soman increases neuronal COX-2 levels: Possible link between seizures and protracted neuronal damageNeuroToxicology, 2010
- Neuropsychological and psychiatric functioning in sheep farmers exposed to low levels of organophosphate pesticidesNeurotoxicology and Teratology, 2010
- Behavioral sequelae following acute diisopropylfluorophosphate intoxication in rats: Comparative effects of atropine and cannabinomimeticsNeurotoxicology and Teratology, 2010
- Heterogeneity of Microglial Activation in the Innate Immune Response in the BrainJournal of Neuroimmune Pharmacology, 2009
- Enhanced microglial activation and proinflammatory cytokine upregulation are linked to increased susceptibility to seizures and neurologic injury in a ‘two-hit’ seizure modelBrain Research, 2009
- Acetylcholinesterase inhibitors and Gulf War illnessesProceedings of the National Academy of Sciences of the United States of America, 2008
- Management of acute organophosphorus pesticide poisoningThe Lancet, 2008
- Long-term event-related potential changes following organophosphorus insecticide poisoningClinical Neurophysiology, 2008