Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 May 12:12:674325.
doi: 10.3389/fphar.2021.674325. eCollection 2021.

Neuroinflammation as a Therapeutic Target for Mitigating the Long-Term Consequences of Acute Organophosphate Intoxication

Peter M Andrew  1 , Pamela J Lein  1
Affiliations
Review

Neuroinflammation as a Therapeutic Target for Mitigating the Long-Term Consequences of Acute Organophosphate Intoxication

Peter M Andrew et al. Front Pharmacol. .

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.

Keywords: acquired epilepsy; astrocytes; cognitive impairment; functional polarization; glial cell activation; microglia.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Upon insult, microglia and astrocytes can adopt a variety of phenotypes associated with different functions. This schematic presents one model of the functional polarization of microglia and astrocytes following acute OP intoxication illustrating a continuum from the extreme pro-inflammatory to anti-inflammatory state. There is some evidence of phenotypic diversity of microglia and astrocytes in animal models of acute OP intoxication (Maupu et al., 2021). Figure created with BioRender.com.
FIGURE 2
FIGURE 2
Proposed temporal profile of the neuroinflammatory response to acute OP intoxication. The shaded area depicts the development of chronic neurological sequelae.
See this image and copyright information in PMC

References

    1. Adams K. L., Gallo V. (2018). The Diversity and Disparity of the Glial Scar. Nat. Neurosci. 21 (1), 9–15. 10.1038/s41593-017-0033-9 - DOI - PMC - PubMed
    1. Alshelh Z., Albrecht D. S., Bergan C., Akeju O., Clauw D. J., Conboy L., et al. (2020). In-vivo Imaging of Neuroinflammation in Veterans with Gulf War Illness. Brain Behav. Immun. 87, 498–507. 10.1016/j.bbi.2020.01.020 - DOI - PMC - PubMed
    1. Angoa-Pérez M., Kreipke C. W., Van Shura K. E., Thomas D. M., Van Shura K. E., Lyman M., et al. (2010). Soman Increases Neuronal COX-2 Levels: Possible Link between Seizures and Protracted Neuronal Damage. NeuroToxicology 31 (6), 738–746. 10.1016/J.NEURO.2010.06.007 - DOI - PMC - PubMed
    1. Aronica E., Crino P. B. (2011). Inflammation in Epilepsy: Clinical Observations. Epilepsia 52 (Suppl. 3), 26–32. 10.1111/j.1528-1167.2011.03033.x - DOI - PubMed
    1. Baik E. J., Kim E. J., Lee S. H., Moon C. (1999). Cyclooxygenase-2 Selective Inhibitors Aggravate Kainic Acid Induced Seizure and Neuronal Cell Death in the hippocampus. Brain Res. 843 (1-2), 118–129. 10.1016/s0006-8993(99)01797-7 - DOI - PubMed