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, drawing parallels to other models of SE. 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.
Highlights
Organophosphates (OPs) are a group of compounds originally synthesized in the 1930s as insecticides
Neuroinflammation refers to the immune-mediated, microglial and astrocyte-propagated responses organized within the nervous system in response to injury in the brain or systemic inflammation (Kraft and Harry 2011; Viviani et al, 2014). This hypothesis derives in part from increasing evidence over the past decade demonstrating that acute OP intoxication triggers robust neuroinflammatory responses that develop within hours and can persist for weeks to months post-exposure, preceding and/or coinciding with the onset of long-term effects
In situations with robust and potentially shifting profiles of microglial activation, it is likely that the functional polarization of microglia critically influences the functional polarization of astrocytes, and the general direction of the neuroinflammatory response following acute OP intoxication
Summary
Organophosphates (OPs) are a group of compounds originally synthesized in the 1930s as insecticides. This hypothesis derives in part from increasing evidence over the past decade demonstrating that acute OP intoxication triggers robust neuroinflammatory responses that develop within hours and can persist for weeks to months post-exposure, preceding and/or coinciding with the onset of long-term effects.
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