A rat model of organophosphate-induced status epilepticus and the beneficial effects of EP2 receptor inhibition.

Neurobiology of Disease
Asheebo RojasRaymond Dingledine

Abstract

This review describes an adult rat model of status epilepticus (SE) induced by diisopropyl fluorophosphate (DFP), and the beneficial outcomes of transient inhibition of the prostaglandin-E2 receptor EP2 with a small molecule antagonist, delayed by 2-4 h after SE onset. Administration of six doses of the selective EP2 antagonist TG6-10-1 over a 2-3 day period accelerates functional recovery, attenuates hippocampal neurodegeneration, neuroinflammation, gliosis and blood-brain barrier leakage, and prevents long-term cognitive deficits without blocking SE itself or altering acute seizure characteristics. This work has provided important information regarding organophosphate-induced seizure related pathologies in adults and revealed the effectiveness of delayed EP2 inhibition to combat these pathologies.

Citations

Feb 11, 2020·Annals of the New York Academy of Sciences·Marson PutraThimmasettappa Thippeswamy
Feb 25, 2020·Annals of the New York Academy of Sciences·Meghan GageThimmasettappa Thippeswamy
Sep 23, 2020·Annals of the New York Academy of Sciences·Laxmikant S DeshpandeRobert J DeLorenzo
Apr 3, 2020·Annals of the New York Academy of Sciences·Marcio De Araujo FurtadoMaria F M Braga
Jan 8, 2021·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Asheebo RojasThota Ganesh
May 1, 2021·International Journal of Molecular Sciences·Claudia Espinosa-GarciaAsheebo Rojas
Jul 27, 2021·Current Opinion in Toxicology·Yi-Hua Tsai, Pamela J Lein
Aug 6, 2021·Journal of Medicinal Chemistry·Madison N SluterJianxiong Jiang
Apr 24, 2020·ACS Chemical Neuroscience·Chunxiang JiangRay Dingledine

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