Andrew Peter M, Lein Pamela J
Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA, United States.
Front Pharmacol. 2021 May 12;12:674325. doi: 10.3389/fphar.2021.674325. eCollection 2021.
Acute intoxication with organophosphates (OPs) can cause a potentially fatal cholinergic crisis characterized by peripheral parasympathomimetic symptoms and seizures that rapidly progress to (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.
有机磷酸酯（OPs）急性中毒可引发潜在致命的胆碱能危象，其特征为外周拟副交感神经症状和癫痫发作，并迅速进展为癫痫持续状态（SE）。虽然急性OP中毒的当前治疗对策在及时给药时能显著提高生存几率，但不足以保护个体免受慢性神经学后果的影响，如认知缺陷、情感障碍和获得性癫痫。神经炎症被认为与这些长期神经后遗症的发病机制有关。在本综述中，我们总结了目前关于急性OP中毒后神经炎症反应进展的已知情况，并与其他SE模型进行了比较。我们还讨论了针对OP诱导的SE后神经炎症的研究，并解释了为何此类治疗干预仅部分改善长期结局且效果不一的可能原因。最后，我们提出了未来治疗策略的发展方向，这些策略旨在针对神经炎症以减轻急性OP中毒的神经后遗症。
